The second step is the mixing of both the aqueous phase and the oily phase by adding either the dispersed phase to the continuous phase, or the continuous phase to the dispersed phase. The effect of the addition order and the addition rate on the drug product quality should be evaluated during process development.


The third step is the introduction of the active substances into the mixture. Some active pharmaceutical ingredients can be dissolved at high temperatures but  recrystallize  during the cooling stage after mixing. To prevent recrystallization, the active substances can be carried to the cooled down cream base via a powder induction system or through slurry addition. The active substances are simultaneously mixed into the cream base.


The last step is the  homogenization  stage.  Agitators , mechanical mixers, rotor stators,  homogenizers , or ultrasonic devices can be employed to ensure uniform excipient  dispersion  and droplet size reduction. Critical variables of the homogenization equipment include time, temperature, and mechanical energy. Critical parameters must be controlled to produce products of consistent quality. [ 2 ] [ 15 ]


A wide spectrum of drugs is available as topical cream formulations. Therefore, topical cream formulations are used to treat many skin diseases.


and  Immunomodulatory  Agents


Cream, together with  gel  and  ointment , are semisolid dosage forms intended for topical application. [ 16 ]  They have different appearances, advantages, disadvantages, and applications.


Topical gels  are a  topical  drug delivery  dosage form  commonly used in cosmetics and treatments for skin diseases because of their advantages over cream and ointment. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  They are formed from a mixture of  gelator , solvent, active drug, and other excipients, and can be classified into  organogels  and  hydrogels . [ 1 ] [ 5 ] [ 6 ] [ 7 ]  Drug formulation and preparation methods depend on the properties of the gelators, solvents, drug and excipients used. [ 1 ] [ 2 ] [ 5 ] [ 3 ] [ 8 ]


A  gel  refers to the semi-


solid, 3-dimensional matrix formed from an interspersed system of colloidal particles or the permeation of a solvent into an entwined polymer chain network. [ 1 ] [ 2 ] [ 5 ] [ 3 ] [ 8 ]  Pharmaceutical gels are formed by adding a  gelator  (gelling agent) to the solvent  [ 5 ] [ 6 ]  and active ingredient mixture.


Gelators used in gel formulation can be small molecules with low molecular weight or polymers (synthetic, semi-synthetic or natural). [ 5 ] [ 7 ]  The solvent that is used as a dispersion medium can be aqueous, organic, inorganic, or a system of different solvents. [ 5 ]


Topical gels are used as a contact or transport medium for active drugs to act on [ 4 ]  or through the skin. [ 9 ]  The active drug molecules are entwined into the 3D mesh of the gel and delivered to the site of action.


Gels have certain special properties that put them apart from other dosage forms, in terms of swelling,  syneresis ,  ageing ,  rigidity  and  rheology .


Gels can be classified through a variety of criteria such as their nature of the  colloidal  phase, nature of the solvent used and physical nature.


This is the most widely used classification of gels. They are classified into two main groups by the nature of the solvent: organogels and hydrogels.


Organogels  are not as commonly used as mediums for drugs or vaccines when compared to other gel classes. [ 5 ]  This is due to the untested or pharmaceutically unacceptable solvents and gelators commonly used in organogel synthesis. [ 5 ]  Organogels that are used pharmaceutically include  microemulsion -based gels and lecithin gels. [ 5 ]


Some manufacturers decide to use organogels as a medium for drug delivery due to its potentially  emollient  effect. Some organogels contain bases composed of  oleaginous  substances. [ 1 ] [ 6 ]  These bases can help retain skin moisture through the formation of an occlusive layer on the area of application. [ 1 ] [ 6 ]  This occlusive layer traps moisture, allowing hydration of the skin and providing an emollient effect. [ 1 ] [ 6 ] [ 10 ]  This emollient effect is particularly helpful in formulation of topical gels for patients with dry and irritated skin. [ 1 ]


Hydrogels  have a high water content, [ 7 ]  with some hydrogels containing up to 90% water. [ 5 ]  Active drugs and other substances dispersed as  colloids  or dissolved in water can be easily taken up by hydrogels. [ 5 ]  Hydrogels are  biocompatible . [ 5 ] [ 7 ]  They also swell to a greater volume than organogels when in contact with water and other natural liquids. [ 8 ]


Hydrogels can be used as drug delivery vehicles, for  transdermal  application,  ophthalmic  drug delivery, [ 11 ]  cancer treatment  [ 12 ]  or for  wound dressing . [ 7 ] [ 13 ]


As a type of water based formulation, hydrogels are generally less greasy and are easier to be removed than oil-based formulations like organogels. [ 6 ]  Examples of hydrogels include aluminum oxide gels, and  bentonite magma . [ 1 ]


Drugs administered through topical application can act locally or systemically. [ 1 ] [ 6 ]  However, the drug molecules must first be retained in and penetrate the surface layer of the  skin . [ 6 ]


Absorption of the drug through the skin surface is a passive process of  diffusion . [ 1 ] [ 9 ]  Skin penetration of the drug can take place by  passive diffusion  directly through the  epidermis  (via  transcellular  or  intercellular  routes), or absorption through  shunt routes  (diffusion through  hair follicles  and  sweat glands ). [ 1 ] [ 6 ] [ 10 ]  Initially, drug absorption may take place via the transfolliar route. After the drug reaches a steady state, transepidermal absorption may replace transfolliar absorption as the main pathway for absorption. [ 1 ]


Drug absorption through the skin varies depending on the concentration gradient between the surface of the skin and the body, [ 1 ] [ 14 ]  with a higher rate of absorption resulting from a greater concentration gradient. [ 6 ] [ 14 ]  The rate of drug absorption can be maintained at a constant level by ensuring that the drug concentration at the surface of the skin remains consistently and substantially greater than that in the body. [ 1 ]


The rate of penetration of the drug across the skin barrier depends on the physiological factors, physicochemical properties of the drug, and gel characteristics. [ 1 ] [ 6 ]  Physiological factors include skin properties, [ 3 ] [ 1 ] [ 2 ]  size of application area, frequency and force of application. [ 1 ] [ 6 ]  Physicochemical properties of the drug include drug solubility, attraction to the skin and  metabolism . [ 3 ] [ 1 ] [ 6 ] [ 10 ]  Gel characteristics include stability,  thermodynamic activity , and  occlusive  properties. [ 3 ] [ 1 ] [ 10 ]


Following penetration through the skin barrier, the drug may permeate through deeper skin tissues and reach the blood capillaries in the  dermis . [ 6 ] [ 9 ]  It may then proceed to enter the  systemic circulation  for systemic effect. [ 1 ] [ 6 ] [ 9 ]


Formulation of topical gels is determined by important factors such as appearance, odor, spreadability, extrudability, viscosity, pH, texture, microbial contamination potential and  bioavailability . [ 1 ]  The components of the vehicle should serve to make the skin surface more penetrable to the drug. [ 1 ]


Characteristics of the gel such as  consistency  and  viscosity  are affected by formulation design. [ 3 ]  Consistency and viscosity affect the adhesion and retention property of the gel, and are important in ensuring the gel is retained at the site of application and effective delivery of the drug. [ 3 ]


The ingredients in topical gel formulation can be broadly categorized into four types: gelator, solvent, drug, and excipients.


Gelators  serve as stabilizers and thickeners, thickening the gel solution while simultaneously maintaining the gel’s flexible nature. [ 8 ]  When dispersed through the solvent as a colloid, gelators offer a stable internal structure to the gel. [ 8 ]  Gelators are usually chosen based on their affinity for the solvent and the purpose of the gel. [ 5 ]  The nature of the gelators used determines the rigidity of the gel. [ 8 ]


There are many types of gelators, of which  carbomers  are more frequently used due to their ability to thicken gels across a wide range of pH. [ 8 ]


Gelators can be classified by polymer types, namely natural, semi-synthetic and synthetic polymers. [ 8 ]


Natural gelators include  tragacanth , [ 6 ]   gelatin ,  collagen , [ 4 ]  and  guar gum ; semi-synthemic gelators include  methylcellulose  and other cellulose derivatives; [ 5 ] [ 8 ] [ 6 ]  while synthetic gelators include  carbomers , [ 6 ]   polyvinyl alcohol ,  polyethylene  and its copolymers. [ 5 ]


Solvents are usually chosen based on the applications of the gel. [ 5 ]  They can be  hydrophilic ,  lipophilic , or  organic . [ 5 ]  Individual solvents can be used alone or as a mixture. [ 5 ]


Some examples of solvents include  purified water , [ 3 ]   glycerin ,  glycols ,  alcohols ,  sucrose ,  toluene , and  mineral oils . [ 5 ] [ 10 ]


Topical  delivery is often used for drugs that are easily degraded in the  GI tract , or are highly susceptible to  hepatic first pass effect . [ 1 ] [ 2 ]  Even if the drug has to be administered for long periods of time or can induce  adverse drug reactions  in parts of the body other than the target location, it can still be formulated as a topical gel. [ 1 ] [ 9 ]


There are a number of physicochemical and biological properties that determine whether a drug is suitable for being delivered topically through a gel dosage form.


Physicochemical properties:


The drug must:


Biological properties:


Excipients  are materials inert to the drug, which are added into dosage forms to improve the overall quality of the dosage form. [ 14 ]  Some examples include  antioxidants ,  sweetening agents ,  stabilizers ,  dispersing agents ,  penetration enhancers ,  buffers  and  preservatives . [ 5 ] [ 3 ]


Penetration enhancers  are excipients that can increase skin permeability. [ 1 ] [ 6 ]  Many classes of excipients can be used as penetration enhancers, such as  glycerin ,  sulfoxides  and related analogues,  pyrrolidines ,  fatty acid  and  ethanol ,  surfactants  etc. [ 1 ] [ 6 ]


Buffers  can be added to control the pH of aqueous or hydroalcoholic based gels. [ 3 ] [ 9 ]  Examples of buffers include  phosphate  and  citrate . [ 3 ]


Preservatives  are important for their  antimicrobial  action, [ 5 ] [ 3 ]  and are especially important in formulation of hydrogels. [ 5 ]  Examples of preservatives include  parabens  and  phenolics . [ 3 ]


Antioxidants  are used to prevent gel ingredients from being  oxidised . [ 3 ]  When choosing the antioxidant to be used, it is important to consider the nature of the solvent. [ 3 ]  Since the solvent of most gels are aqueous in nature, water-soluble antioxidants are more commonly used. [ 3 ] Some common examples include  sodium metabisulphite  and sodium formaldehyde sulfoxylate. [ 6 ]


Sweetening agents are only used in gels that are designed to be used in the oral cavity such as dental gels. [ 3 ]  Examples include  sucrose ,  glycerol ,  sorbitol  and liquid  glucose . [ 3 ]


The process of gel formation involves finding a balance between the concentrations of the gelator and the solvent. [ 5 ]  When adding a gelator to the solvent, the mixture remains in liquid state. [ 5 ]  As the concentration of the gelator increases to a certain critical concentration (gelling point),  gelation  occurs through swelling to form the semi-solid gel. [ 5 ]  Further increasing the concentration of the gelator beyond the gelling point will increase gel viscosity. [ 5 ]


The exact gelling point varies depending on the properties of the gelator and the solvent, such as structure uniformity, molecular weight of the polymer, and flexibility of the polymer chain. [ 5 ]


Generally, gels are prepared by firstly dissolving the soluble excipients in the solvent. [ 5 ] [ 3 ]  The solution is then mixed using a mechanical stirrer. [ 3 ]  After that, the gelator is added slowly to the stirred mixture in order to avoid aggregation. [ 3 ]  Then, the mixture is continuously stirred until the polymer dissolves and a gel gradually forms. [ 3 ]  The gel is allowed to settle for one to two days before the final consistency of the gel can be reached. [ 5 ]


The exact method of preparing gels depends on the properties of the formulation ingredients.


Topical gels are commonly used as  sustained release dosage forms . [ 5 ] [ 9 ]  Usage of the sustained release dosage form reduces the administration of recurrent doses while maintaining  serum  dose levels at the therapeutic range (difference between toxic and therapeutic doses), hence improving  patient compliance . [ 5 ]


Some topical gels are fast release gels, which are highly absorbent and can swell rapidly. [ 5 ]  These fast release gels can be used to treat acute disorders.


Topical gels are also used as  lubricants , or carriers for pharmaceutical agents. [ 5 ]  They can be used as vehicles for different purposes, via different routes of administration, such as dental,  dermatological [ 15 ] l , [ 16 ] [ 17 ]   ophthalmic , [ 11 ]  intranasal, vaginal, rectal and others. [ 5 ] [ 1 ] [ 2 ] [ 8 ]


Topical gels are commonly used in cosmetics, which include shampoos,  dentifrices , skin and hair care formulations and fragrance products, [ 1 ] [ 2 ]  and can be used to treat scalp inflammation. [ 2 ]


Topical gels can be used to deliver  anti-inflammatory   steroids  to the scalp in treatment of scalp inflammations. [ 8 ]


Examples of Commercially available topical gels.   [ 6 ]


The texture of topical gels is less greasy as it contains a higher proportion of water compared with cream and  ointment . [ 3 ] [ 1 ] [ 2 ] [ 8 ]  These gels have an excellent spreading property and cooling effect due to solvent evaporation, and also has a higher retention time on the skin. [ 5 ] [ 3 ] [ 1 ] [ 2 ] [ 8 ]  Topical gels are more stable than creams and ointments, and can adhere well to the site of application. [ 5 ] [ 2 ]  They form an occlusive layer on the application site that can act as a form of protection. [ 5 ]  They can be washed off easily and are nontoxic due to their unique composition and structure. [ 5 ] [ 2 ] [ 6 ]  They have minimal side effects due to their localized effect. [ 1 ]  Topical gels are convenient and easy to apply. [ 2 ] [ 6 ]  The topical mode of action of topical gels is also  non-invasive . [ 1 ] [ 6 ]  These favorable factors of topical gels improve patient  compliance  and  tolerability . [ 1 ] [ 2 ]


The formulation and manufacturing processes of topical gels are relatively simpler and more cost effective than other semisolid dosage forms. [ 5 ] [ 1 ] [ 8 ]  The release profile of the gel can be modified by altering the properties of the gelator, allowing for continuous drug delivery. [ 1 ]  Topical gels are also eco-friendly,  biocompatible  and  biodegradable . [ 5 ] [ 8 ]


The drug can penetrate deeply into the skin  [ 2 ]  and be directly delivered to the target site, as the topical application allows it to avoid  hepatic first pass metabolism . [ 1 ] [ 2 ] [ 8 ] [ 6 ]  Difficulties in gastrointestinal absorption caused by pH, enzymatic activity and drug-food interactions can be minimized, while at the same time avoiding GI irritation. [ 1 ] [ 2 ] [ 6 ]  The topical dosage form allows stable and continuous drug delivery to the site of application, [ 2 ]  while having a faster drug release than ointments and creams. [ 1 ]  All these can increase the drug’s  bioavailability  in the body. [ 2 ]


There may be  flocculation  in some gels, which may produce an unstable gel. [ 5 ] [ 8 ]  The  rheology  of some gels are easily altered by environmental factors such as temperature and humidity, [ 5 ]  resulting in stricter storage requirements.  Syneresis  of the gel may occur during storage, causing the gel to shrink unpredictably or even dry out. [ 5 ] [ 3 ]  The gelators may precipitate and  salt out , and some drugs may degrade in gel formulation due to the other ingredients present in the formulation. [ 5 ]


Some additives and gelators added into the formulation may cause irritation problems, [ 5 ] [ 8 ]  such as skin irritation,  dermatitis  or  allergic conditions . [ 2 ]  The increased water content in gels increases the chances of microbial or fungal attack, [ 5 ] [ 8 ]  which may contaminate the gel, making it unsuitable for use. Considering the direct route of administration, drugs must be very small in size to have an effective plasma concentration for action. The particle size and other properties of the drug may also affect its absorption through the  skin  barrier, [ 2 ]  resulting in an unreliable effect.


Transdermal implants , or  dermal piercings , are a form of  body modification  used both in a  medical  and  aesthetic  context that, in contrast to  subdermal implants , consist of an object placed partially below and partially above the  skin , thus  implanted   trans dermal. Two techniques are prevalent using  post -like and microdermal implants respectively.


Although the skin around such implants generally heals as if it were a  piercing , in the body piercing community, these types of modification are commonly called fairly "heavy" due to the complexity of the procedure, but the potential  social implications  either.


When the procedure is done using a  post -like implant, an incision is made a small distance from the site. The skin is then lifted and the implant is passed through. Then, a hole is opened at the site for it to pass through, and it is moved so that the top part fills the hole. The implants used for this are generally small and not textured in any way except rounding.


If a more graphic implant is desired, it is generally done in two parts. First, the base is inserted the same way a single-part would be, except that the base implant is threaded. It may either stick out like a bolt, or be inward like a nut. When this is done, the top half is screwed on. This type is usually done for spikes and/or horns.


In any case, the part of the implant which passes under the skin generally is somewhat large and has holes. The skin will grow into them, making it more permanent.


Microdermal implants  are a form of  body modification  which gives the aesthetic appearance of a transdermal implant, without the complications of the much more complicated surgery associated with transdermal implants. [ 1 ] [ unreliable source? ]  Microdermals are single point piercings which are a sort of surface piercing. [ 2 ]


Microdermal implants can be placed practically anywhere on the surface of the  skin  on the body, but are different from conventional  piercings  in that they are composed of two components: an anchor, which is implanted underneath the skin, with a step protruding from (or flush with) the surface of the surrounding skin, and the changeable  jewellery , which is screwed into the threaded hole in the step of the anchor.


They should not be implanted in hands, feet, wrists, collarbones or any area where it is not flat or that is near a joint. [ 3 ]


The procedure is usually performed using a dermal punch or needle. When a dermal piercing is done with a punch, the pouch is made in a different way. When using a needle, the pouch is made by separating the skin. When using a dermal punch, the pouch is made by removing a bit of tissue. A microdermal punch is less painful and therefore commonly used. The process starts by identifying the point of piercing on the sterilized area that will be marked with a surgical marker. The microdermal punch is then used to remove skin tissues. The anchor is then placed under the skin and a piece of jewelry is placed using surgical forceps. [ 4 ]


A  metered-dose transdermal spray  ( MDTS ) delivers a  drug  to the surface of the skin and is absorbed into the circulation on a sustained basis. It works in a similar manner to a  transdermal patch  or  topical gel . The drug is delivered by a device placed gently against the skin and triggered, causing it to release a light spray containing a proprietary formulation of the drug that quickly dries on the skin to form an invisible drug depot. As it would be from a patch, the drug is then absorbed steadily for a predetermined amount of time.


Transfersome  is a proprietary drug delivery technology, an artificial  vesicle  designed to exhibit the characteristics of a  cell vesicle  suitable for controlled and potentially targeted drug delivery. Some evidence has shown efficacy for its use for drug delivery without causing skin irritation, [ 1 ]  potentially being used to treat skin cancer. [ 2 ]  Transfersome is made by the German company IDEA AG.


Ultrasound-triggered drug delivery using stimuli-responsive hydrogels  refers to the process of using  ultrasound  energy for inducing drug release from  hydrogels  that are sensitive to acoustic stimuli. This method of approach is one of many  stimuli-responsive drug delivery-based systems  that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as  COVID-19 , there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.


Hydrogels are three dimensional structures consisting of hydrophilic  polymers  (i.e., polymers, colloids, etc.) that form networks through cross-linking processes. The macromolecules involved in the formation of hydrogels are able to absorb and retain large amounts of water and other aqueous substances. Since its discovery in 1960, [ 1 ]  hydrogels have become a crucial component in biomedical research and applications. A few examples of hydrogel use include organ regeneration, [ 2 ]   wound healing , [ 3 ] [ 4 ] [ 5 ]  and  drug delivery . [ 6 ] [ 7 ]  Hydrogels are generally classified based on the following characteristics: material, crosslinking mechanism, physical structure, electric charge, and response to stimuli. [ 8 ]  Synthesis of hydrogels are developed from a combination or isolated forms of natural and synthetic polymers. [ 2 ] [ 9 ]  The main examples of natural polymers used to derive hydrogels include polysaccharides, [ 9 ]  polypeptides, [ 10 ]  and polynucleotides. [ 5 ]  Several known examples of synthetic polymeric constituents include poly (vinyl alcohol) ( PVA ), [ 7 ] [ 9 ] [ 11 ]  poly (acrylic acid) ( PAA ), [ 7 ] [ 9 ] [ 11 ]  and poly (2-hydroxyethyl methacrylate) ( PHEMA ). [ 9 ] [ 11 ] [ 12 ] [ 13 ]  The crosslinking mechanism of the hydrophilic macromolecules are driven by covalent bonding, resulting in a physical- or chemical-type hydrogel. Physical hydrogels contain reversible matrices of hydrogen and non-covalent bonds, while chemical hydrogels are composed of irreversible matrices that are molecularly held together by covalent bonds. Used as another parameter in characterizing gels,  electric charge  (also referred to as ionic character) describes the ability of the macromolecules to drive swelling behavior. Hydrogels classified based on this property fall under three main categories: cationic, anionic, and amphoteric. Bawa et al. demonstrated that cationic gels swell in acidic environments but remain condensed in basic environments. [ 14 ]


Since traditional hydrogels were able to encapsulate and carry materials, research into drug-loaded hydrogels began to expand in the field of drug delivery. Dubbed as “smart hydrogels” or “stimuli-responsive hydrogels”, these gels are able to dynamically respond to external or internal stimuli in addition to possessing similar swelling-deswelling properties of traditional hydrogels. Various examples of external stimuli that have been used to control smart hydrogels in drug delivery systems include temperature, [ 10 ] [ 12 ] [ 13 ] [ 15 ] [ 16 ] [ 17 ]  pH, [ 12 ] [ 13 ] [ 15 ] [ 16 ] [ 17 ]  light, [ 10 ] [ 12 ] [ 15 ] [ 16 ]  ultrasound, [ 15 ] [ 16 ]  and enzymes. [ 18 ]  Additional considerations in designing smart hydrogels involve fundamental understanding of  bond strength , molecular weight, degree of polymerization, polymer structure, and molecular assembly. [ 17 ] [ 19 ]  The bond strength describes the cross-linking strength of the hydrogel, which is considered in designing drug release mechanisms of hydrogel-based platforms. Scientific understanding of the molecular weight of gels is taken into account when loading drugs of increasing weight. [ 20 ]  Similar to conventional hydrogels, the polymeric chain (or backbone) of the smart hydrogels is derived from  polysaccharides ,  polypeptides , and polynucleotides. Examples of natural polymers include  alginate , [ 21 ] [ 22 ] [ 23 ]   chitosan , [ 6 ] [ 17 ] [ 24 ] [ 25 ]   cellulose , [ 6 ] [ 13 ]   gelatin , [ 13 ]   fibrin , [ 17 ]  and  collagen . [ 26 ]  Hydrogel size and type are the two main properties considered in designing hydrogels when seeking the optimal delivery route for drug administration. [ 27 ]  Various examples of hydrogel type designs include  nanoparticles , [ 13 ] [ 28 ]   nanogels , [ 16 ] [ 28 ] [ 29 ]  and microgels. [ 29 ]  For example, El-Sherbiny et al. proposed gelatin-based hydrogel nanoparticles that were stimulated by magnetic forces. [ 30 ]  Other variables considered in hydrogel design include safety, biodegradability, [ 31 ]  drug loading capacity, and on-demand control of drug release [23]. The main safety concerns in formulating hydrogels include bacterial infection [ 32 ]  and biocompatibility. [ 26 ]  The final parameter considered in developing hydrogels for drug delivery systems revolve around the embedded payload within the hydrogel. [ 33 ]  Cells, proteins, and therapeutic drugs are the main payloads used in hydrogel-based drug delivery platforms. [ 34 ]  In one example of payload use, Jiang et al. demonstrated the stimulated release of  gallic acid  from chitin-based hydrogel via ultrasound induction. [ 24 ]


According to the Moyano et al., ultrasound refers to vibrational mechanical waves with frequencies greater than 20 kilohertz (kHz). [ 35 ]  Ultrasound is traditionally used for imaging, monitoring, and diagnosing a broad range of conditions in the medical field. Various examples of ultrasound modalities include Doppler ultrasound, focused ultrasound, and echocardiography. The key component of using most ultrasound devices is a transducer that consists of an array of piezoelectric crystals. The atoms within these crystals vibrate under electrical current stimulation, converting this electrical energy into mechanical, in this case, high acoustic or ultrasonic energy. When the sonicating transducer is directed at the human body, the resulting sound pressure waves produced by the transducer will pass through the dermal layer and reach the tissue where the waves are reflected (or echoed) back to the transducer and converted back into electrical signals for image reconstruction. Tissue characteristics such as density affect the intensity of the reflected sound waves. Other parameters such as beam frequency, equipment components, and imaging settings contribute towards the resolution of the ultrasound application. Ultrasound has also been used for therapeutic purposes because it is non-invasiveness, able to provide deeper tissue penetration, and safely localize application of acoustic energy. [ 19 ]


While ultrasound modalities are generally considered safe, extreme levels of human exposure to ultrasound can increase injury risk. [ 35 ]  In the US, the  Food and Drug Administration  (FDA) guidelines, [ 34 ]  the maximum allowed exposure to ultrasound for use is defined by the following key parameters:  mechanical index , [ 36 ]  thermal index, [ 37 ]  spatial-peak temporal-peak intensity, [ 38 ]  spatial-peak pulse-average power, [ 39 ]  and spatial-peak temporal-average power. [ 34 ]  Mechanical index (MI) is a unitless metric that is used to measure the acoustic power output from ultrasound use. Since the MI is inversely proportional to the ultrasonic beam frequency, the MI will be lower at higher frequencies. The thermal index (TI) describes the risk of increasing the temperature of the tissue being sonicated by ultrasound. A solution to decreasing TI involves the reduction of the time that the sonicating transducer is focused on the targeted area. [ 37 ]  The spatial-peak temporal-peak (SPTP) power refers to the highest intensity output of the ultrasound beam during implementation. The spatial-peak pulse-average (SPPA) power is a measure of the maximum intensity output averaged over the duration of ultrasound use in. The spatial-peak temporal-average power describes the measure of the highest intensity output generated by the repeating pulse of the ultrasound beam over a period of time.


Due to the sonication capability of ultrasound and drug-release property of smart hydrogels, there has been scientific interest in controlling the release of the payload from hydrogels. [ 10 ]  Focusing and directing acoustic energy (that can convert to thermal or mechanical energy [ 36 ] [ 40 ] ) towards smart hydrogels, implanted within tissue at times, induces a hydrogel response that results in the release of the embedded payload. Although hydrogels that are sensitive to mechanical pressure are generally used in ultrasound-triggered drug delivery platforms, hydrogels that respond to changes in temperature have also been used for these systems. [ 10 ]   For example, Makhmalzadeh et al. proposed an ultrasound-triggered drug delivery method involving the use of thermo-responsive hydrogels loaded with  silibinin , a cancer drug for treating melanoma. [ 16 ] [ 41 ]  At low temperatures, these thermo-responsive hydrogels exist in liquid form but following ultrasonication, they transition into a gel state. [ 16 ] [ 25 ]  Although ultrasound- and thermo-sensitive hydrogels are responsive to certain ultrasound modalities, they differ in how they respond to external stimuli. Ultrasound-responsive hydrogels are capable of being stimulated by more than one type of stimulation force through ultrasound. [ 42 ]  Conversely, thermo-responsive hydrogels, as the name specifies, can only respond to the thermal forces induced by ultrasound. [ 13 ]  Despite this, thermo-responsive hydrogels have been widely used in cancer-based drug delivery systems. [ 6 ]


Of the existing ultrasound modalities, focused ultrasound has been used extensively in drug delivery research. [ 33 ] [ 34 ]  High-Intensity Focused Ultrasound (HIFU) and Low-Intensity Focused Ultrasound are the two main techniques used in inducing drug release from smart hydrogels. [ 43 ]  Current HIFU applications are used for ablating tumors located at increased depths. [ 44 ]  Since HIFU is able to invoke high temperatures, they have been used for cancer therapy by stimulating drug release from smart hydrogels via thermolysis mechanisms. [ 45 ]  In regard to the use of ultrasound- and thermo-responsive hydrogels for drug delivery, HIFU is able to stimulate both types of hydrogels. [ 45 ]  In one study related to cancer therapy, HIFU exhibited high efficiency inducing nanovaccine release from hydrogel-based carriers. [ 46 ]  Although HIFU has been studied in various capacities, this technique can cause irreparable damage to healthy tissue. [ 31 ]  Therefore, LIFU has been the conventional method for use in hydrogel responsive drug delivery platforms. In other areas of the biomedical field, LIFU has been used for stimulation such as bone regeneration in  tissue engineering  applications. [ 47 ] [ 48 ]  Due to its lower generated acoustic power output, LIFU is preferred over HIFU in biomedical applications involving neuromodulation [ 49 ]  and other brain-related procedures. [ 50 ]  Studies have shown that LIFU has proven to be a cost-effective and non-invasive method for hydrogel-based drug delivery. [ 51 ]


The underlying drug-releasing mechanism induced by focused ultrasound onto ultrasound-sensitive hydrogels is based on mechanical or thermal effects. [ 19 ] [ 31 ] [ 45 ]  Mechanical-based ultrasound sonication mechanisms refer to the conversion of acoustic energy into mechanical energy with various types that include acoustic cavitation force, [ 31 ] [ 45 ]  or oscillation force. [ 36 ]  Generally, applying mechanical pressure to a responsive hydrogel loaded with drugs causes the hydrogel to deform. This deformation reduces the structural integrity of the hydrophobic core, allowing for the release of the drug payload. [ 43 ]  Both ultrasound- and thermo- responsive hydrogels are capable of carrying various embedded carriers of drug payloads which include metal-organic framework, [ 52 ]  nanoparticles, [ 23 ] [ 28 ]  and liposomes. [ 53 ]  Although many studies have demonstrated the irreversible compression of hydrogels induced under ultrasound, Goncalves et al. designed hydrogel-based nanoparticles that were capable of “self-healing”, meaning they were able to return to their original form following drug release from its depot. [ 28 ]


Acoustic cavitation forces, specifically, have been used in conjunction with ultrasound-responsive hydrogels for drug delivery. This type of mechanical force refers to the formation, growth, and destruction of bubble occurs that results in the generation of acoustic energy. There are varying degrees of cavitation which divided into three groups:  sonoporation , [ 15 ]  stable cavitation, [ 3 ] [ 15 ] [ 36 ]  and inertial cavitation. [ 19 ] [ 36 ]  Sonoporation refers to the process of using ultrasound to open pores (or permeability) of cellular membranes to allow substances of interest to enter into the targeted cell. In cases where  microbubbles  are coated with hydrogels, these embedded carrier systems undergo stable cavitation and inertial cavitation. [ 36 ]  Stable cavitation characterizes vapor bubbles that oscillate within its own equilibrium, while inertial cavitation describes bubbles that generate a net growth each time the bubble expands and results in the bubble collapsing violently. Severe cavitation increases the risk of damage to tissue and drug degradation. [ 3 ] [ 7 ]  Other forces generated by ultrasound that is used in several hydrogel-based platforms are hyperthermia [ 36 ] [ 45 ]  and radiation. [ 36 ]  These forces are generally created by HIFU as they generate high levels of heat. Thus, guidelines established by the FDA help ensure the safe use of ultrasound in all biomedical applications, inclusive of drug delivery systems, based on the scientific understanding of these mechanical forces.


In regard to tissues, ultrasound is generally used for imaging and monitoring tissue pathologies. [ 34 ]  Due to its ability to penetrate through tissue easily, [ 25 ]  ultrasound has been widely studied and developed for drug delivery applications in the field of tissue engineering. In order for hydrogels to release drugs at the targeted location, they must be injected or implanted within the tissue. Injection of hydrogels is usually preferred over implantation due to its minimal invasiveness, [ 2 ] [ 6 ] [ 25 ]  reduced healing time following the procedure, [ 47 ]  and biocompatibility. [ 54 ]  In one study, Liu et al. proposed a novel design of injectable  chemotaxis  hydrogels to help promote the migration of bone marrow mesenchymal cells for cartilage repair. [ 55 ]  Other examples of using smart hydrogels and ultrasound in tissue engineering applications include cartilage repair, [ 55 ]  bone repair, [ 47 ] [ 56 ]  and wound healing. [ 3 ]  The design of these drug delivery platforms is specific to each tissue type and its intended use. [ 26 ]


In the field of  cancer , ultrasound is commonly used for helping health care professionals detect and develop a diagnosis in affected patients. [ 34 ]  In the context of drug delivery, ultrasound has been used for a wide variety of therapeutic applications which include but are not limited to melanoma, [ 16 ]  ovarian cancer, [ 7 ] [ 16 ]  and breast cancer. [ 16 ] [ 21 ]  Hydrogels are generally used in designing these drug delivery platforms due to minimal invasiveness (if injected) and its ability to carry a different cancer drugs. These hydrogel-based systems are also paired with chemotherapy treatments. [ 45 ]  Cancer drugs used in this drug delivery platforms include  doxorubicin , [ 6 ] [ 21 ] [ 40 ]   mitoxantrone , [ 22 ]   paclitaxel , [ 16 ] [ 57 ]  silibinin, [ 16 ] [ 57 ]  and  cisplatin . [ 16 ] [ 57 ]  In a cancer therapy study, Baghbani et al. proposed a method of pairing ultrasound with doxorubicin-loaded alginate-stabilized perfluorohexane (PFH) nanodroplets. [ 21 ]


Although it is generally used in combination with cancer therapeutic treatments, [ 16 ]  gene therapy has become a topic of interest in the drug delivery field. Gene therapy refers to the insertion of genes into a biological system in an attempt to add or modify mutated genes for therapeutic benefit. In order to attain high  transgene  expression, the  electrostatic  interaction between the gene and hydrogel polymer and the controlled release of the drug payload from the hydrogel is necessary. [ 36 ]  Several gene therapy drugs used in hydrogel-based drug delivery systems include CRISPR/Cas9, [ 58 ]   siRNA , [ 40 ] [ 59 ]  and other RNA-based drugs. [ 59 ]  In a gene therapy study, Han et al. proposed a focused ultrasound-responsive hydrogel-based system for delivering siRNA nanoparticles to the targeted tumor site [ 60 ]


The main challenge for future ultrasound-triggered hydrogel responsive delivery systems is to develop safer guidelines for using HIFU to take advantage of its benefits. In doing so, this will lead to improvements on FDA guidelines for ultrasound use. Therefore, the use of LIFU or lower acoustic energy intensity settings is suggested as the conventional method for decreasing injury risk, specifically damage to healthy tissue, until then. [ 34 ]  Focused ultrasound continues to be the primary type of ultrasound technique used in drug delivery systems. Another challenge presented in using ultrasound for inducing drug release from smart hydrogels in delivery platforms is inappropriate drug administration and unexpected complications. [ 31 ]  Currently, on-demand drug release from ultrasound-responsive hydrogels is still difficult to fully control when only using ultrasound. Yeingst et al. suggested that future hydrogel-based delivery platforms will be designed based on the drug payload to optimize the interaction between the ultrasound and stimuli-responsive hydrogel. [ 34 ]  Future development of drug delivery systems will continue to incorporate ultrasound and smart hydrogel designs.


Uniject  is a disposable, pre-filled, single-use  syringe  which was developed to promote vaccination in developing countries. It was developed by  PATH  as part of the solution to the problem of delivering vaccines to areas which have insufficient medical workers to meet the needs of traditional, doctor-mediated vaccination programs.


The Uniject was invented by PATH in 1987. [ 1 ]


In 2003 PATH accepted a  Tech Award  from  The Tech Museum of Innovation  for its development of the Uniject. [ 2 ]


To activate the device, the user would first shake the device to homogenize the liquid suspension. Then, the  tamper-evident  seal would be twisted. After that, with "a firm, rapid motion" the needle shield would be pushed into the port until the "gap between the needle shield and port closes completely". [ 3 ]  To actually use the device, the needle shield needs to be removed, exposing the needle. The user would then push the needle into the skin. Almost simultaneously, the reservoir would be pushed down in a similar motion to opening a  blister pack  or using a syrette, dispensing the medication through the needle into the skin. [ original research ]  The device, once used, should be considered  sharps waste .


The introduction of the Uniject has been called "the greatest single leap forward in the battle against tetanus" [ 4 ]  because it has allowed tetanus vaccines to be used in places which were previously inaccessible to health programs.


A  unilamellar liposome  is a spherical  liposome , a  vesicle , bounded by a single bilayer of an  amphiphilic   lipid  or a mixture of such lipids, containing aqueous solution inside the chamber. Unilamellar liposomes are used to study biological systems and to mimic cell membranes, and are classified into three groups based on their size: small unilamellar liposomes/vesicles (SUVs) that with a size range of 20–100 nm, large unilamellar liposomes/vesicles (LUVs) with a size range of 100–1000 nm and giant unilamellar liposomes/vesicles (GUVs) with a size range of 1–200 μm. [ 1 ]  GUVs are mostly used as models for biological membranes in research work. [ 2 ]  Animal cells are 10–30 μm and plant cells are typically 10–100 μm. Even smaller cell organelles such as mitochondria are typically 1–2 μm. Therefore, a proper model should account for the size of the specimen being studied. [ 1 ]  In addition, the size of vesicles dictates their  membrane curvature  which is an important factor in studying fusion proteins. SUVs have a higher membrane curvature and vesicles with high membrane curvature can promote membrane fusion faster than vesicles with lower membrane curvature such as GUVs. [ 3 ]


The composition and characteristics of the cell membrane varies in different cells (plant cells, mammalian cells, bacterial cells, etc). In a membrane  bilayer , often the composition of the phospholipids is different between the inner and outer leaflets. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin are some of the most common lipids most animal cell membranes. These lipids are widely different in charge, length, and saturation state. The presence of unsaturated bonds (double bonds) in lipids for example, creates a kink in acyl chains which further changes the lipid packing and results in a looser packing. [ 4 ] [ 5 ]  Therefore, the composition and sizes of the unilamellar liposomes must be chosen carefully based on the subject of the study.


Each  lipid bilayer  structure is comparable to  lamellar phase  lipid organization in  biological membranes , in general. In contrast,  multilamellar liposomes  (MLVs), consist of many concentric amphiphilic lipid bilayers analogous to onion layers, and MLVs may be of variable sizes up to several micrometers.


There are several methods to prepare unilamellar liposomes and the protocols differ based on the type of desired unilamellar vesicles. Different lipids can be bought either dissolved in  chloroform  or as  lyophilized  lipids. In the case of lyophilized lipids, they can be solubilized in chloroform. Lipids are then mixed with a desired molar ratio. Then chloroform is evaporated using a gentle stream of nitrogen (to avoid oxygen contact and oxidation of lipids) at room temperature. A  rotary evaporator  can be used to form a homogeneous layer of liposomes. This step removes the bulk of chloroform. To remove the residues of trapped chloroform, lipids are placed under vacuum from several hours to overnight. Next step is re-hydration where the dried lipids are re-suspended in the desired buffer. Lipids can be vortexed for several minutes to insure that all the lipid residues get re-suspended. SUVs can be obtained in via two methods. Either by  sonication  (for instance with 1 second pulses in 3 Hz cycles at a power of 150 W) or by extrusion. In extrusion method, the lipid mixture is passed through a membrane for 10  or more times. [ 6 ] [ 7 ]  Depending on the size of the membrane, either SUVs or LUVs can be obtained. Keeping vesicles under argon and away from oxygen and light can extend their lifetime.


Natural swelling: in this method soluble lipids in chloroform are pipetted on a Teflon ring. The chloroform is allowed to evaporate and the ring is then placed under the vacuum for several hours. Next the aqueous buffer is added gently over the Teflon ring and lipids are allowed to naturally swell to form GUVs overnight. the disadvantage of this method is that a large amount of multilamellar vesicles and lipid debris are formed.


Electroformation: In this method lipids are placed on a conductive cover glass (indium tin oxide or ITO coated glass) or on Pt wires instead of a Teflon ring and after vacuuming, buffer is placed on the dried lipids and it is sandwiched using a second conductive cover glass. Next an electrical field with certain frequency and voltage is applied which promotes formation of GUVs. For polyunsaturated lipids, this technique can induce a significant oxidation effect on the vesicles. [ 8 ]  Nevertheless, it is a very common and reliable technique to generate GUVs. Modified approaches exist that employ gel-assisted swelling (agarose-assisted swelling or PVA-assisted swelling) for the formation of GUVs under more biologically relevant conditions. [ 9 ]


A variety of methods exist to encapsulate biological reactants within GUVs by using water-oil interfaces as a scaffold to assemble lipid layers. This allows the use GUVs as cell-like membrane containers for the in vitro recreation (and investigation) of biological functions. [ 10 ]  These encapsulation methods include microfluidic methods, which allow for a high-yield production of vesicles with consistent sizes. [ 11 ]


Phospholipid   liposomes  are used as targeted  drug delivery  systems. [ 12 ]   Hydrophilic  drugs can be carried as solution inside the SUVs or MLVs and  hydrophobic  drugs can be incorporated into  lipid bilayer  of these liposomes. If injected into circulation of human/animal body, MLVs are preferentially taken up  phagocytic cells , and thus drugs can be targeted to these cells. For general or overall delivery, SUVs may be used. For topical applications on skin, specialized lipids like phospholipids and   sphingolipids  may be used to make drug-free liposomes as moisturizers, and with drugs such as  for anti-ultraviolet radiation applications.


In biomedical research, unilamellar liposomes are extremely useful to study biological systems and mimicking cell functions. [ 1 ] [ 10 ]  As a living cell is very complicated to study, unilamellar liposomes provide a simple tool to study membrane interaction events such as  membrane fusion , protein localization in the plasma membrane, study ion channels, etc.


Vaginal rings  (also known as  intravaginal rings , or  V-Rings ) are polymeric  drug delivery  devices designed to provide controlled release of drugs for  intravaginal administration  over extended periods of time.  The ring is inserted into the  vagina  and provides contraception protection. Vaginal rings come in one size that fits most people.


Several vaginal ring products are currently available, including:


A number of other vaginal ring products are also in development.


The combined hormonal contraceptive vaginal ring is self-administered once a month. Leaving the ring in for three weeks slowly releases hormones into the body, mainly  vaginally administered estrogens  and/or  progestogens  (a group of hormones including  progesterone ) - the same hormones used in birth control pills. [ 4 ]  These hormones work mostly by stopping ovulation and thickening the cervical mucus, creating a barrier preventing sperm from fertilizing an egg. [ 4 ]  They could theoretically affect implantation but no evidence shows that they do. [ 5 ]  Worn continuously for three weeks followed by a week off, each vaginal ring provides anywhere from one month (NuvaRing) to one year (Annovera and Progering) of birth control. For continuous-use contraception, users can also choose to wear the vaginal ring for the full four week cycle. This manner of contraception will eliminate monthly periods. [ 6 ]  Throughout the additional week, the serum hormone levels will remain in the contraceptive range. [ 7 ]


When compared with combined hormonal pills, the combined hormonal vaginal ring offers potentially better cycle control and treatment of  heavy menstrual bleeding . [ 8 ]  However, both methods are effective short-term treatments in the reproductive age group. Vaginal rings may lead to increased normal vaginal secretions, decreased body weight, reduced symptoms of  PMS , and occasionally cases of  vaginitis , device-related problems and  leukorrhea . [ 4 ] [ 7 ] [ 8 ]  Because they release estrogen, vaginal rings have an increased risk of heart attack, stroke, and other serious side effects. [ 6 ]  Additionally, certain medicines and supplements, such as the antibiotic  rifampin , the anti-fungal  griseofulvin , anti-seizure medicines,  St. John's wort , and  HIV  medicines, may compromise the effectiveness of vaginal rings. [ 6 ]  Vaginal rings do not protect users from  sexually transmitted diseases . The only contraceptive measures that does so are latex or polyurethane  condoms . [ 4 ]


The  contraceptive vaginal ring  has a failure rate of 0.3% when used as prescribed and 9% when used typically. [ 7 ] [ 9 ]


The correlation between breast cancer and the use of vaginal rings is under investigation, but recent literature suggests that the hormones used in vaginal rings has little, if any, relation to the risk of developing breast cancer. [ 6 ]


Vaginal rings are easily inserted and removed. [ 10 ]  Vaginal walls hold them in place. Although their exact location within the vagina is not critical for clinical efficacy, rings commonly reside next to the  cervix , and the deeper the placement in the vagina, the less likely the ring will be felt. [ 6 ] [ 7 ]  Rings are typically left in place during intercourse, and most couples report no interference or discomfort. In many cases, neither partner feels the presence of the ring. [ 11 ]  Rings can be removed prior to intercourse, but, in the case of the contraceptive NuvaRing, only for one to three hours to maintain efficacy of birth control. If the ring is out for more than 48 hours, back up contraception is necessary for seven days. [ 6 ]  It typically takes between one and two months for a user's cycle to return to normal after the use of a vaginal ring is stopped. [ 6 ]


A  vaporizer  or  vaporiser , colloquially known as a  vape , is a device used to vaporize substances for  inhalation . Plant substances can be used, commonly  cannabis ,  tobacco , or other herbs or blends of  essential oil . [ 1 ]  However, they are most commonly filled with a combination  propylene glycol ,  glycerin , and drugs such as  nicotine  (e.g. extract from tobacco) or  tetrahydrocannabinol  as a liquid solution. [ 2 ]


Vaporizers contain various forms of extraction chambers including straight bore,  venturi , or sequential venturi, and are made of materials such as metal or glass. The extracted vapor may be collected in an inflatable bag, or inhaled directly through a hose or pipe. When used properly, cooler temperatures due to lack of combustion [ 3 ]  result in significantly more efficient extraction of the ingredients. Hence, the irritating and harmful effects of smoking are heavily reduced, [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]  as is its  secondhand smoke .


Cannabis flower is commonly consumed using a dry herb vaporizer. The cannabis may be heated in a chamber via indirect flame exposure or an electrical heating element, allowing users to inhale the resulting vapor. The temperatures reached are cooler than the combustion temperature of cannabis, which is around 230–315 °C (445–600 °F). [ 9 ]


Vaporizing is more efficient than  smoking , because approximately 30% of  THC  in cannabis or hashish cigarettes is destroyed by  pyrolysis  during smoking. [ 10 ]


Cannabis is also consumed via the vaporization of  cannabis concentrates  or oils that have been extracted from the plant, commonly referred to as "dabbing". Users typically employ a torch to heat a small cup shaped quartz or titanium attachment on a bong before dabbing the oil onto the heated surface and inhaling the vapors through the bong. [ 11 ]  This route of consumption is generally much more potent than smoking or vaporizing marijuana flower due to the increased concentration of cannabinoids. Users typically report that the effects of dabbing are much more intense than regular cannabis, while also being shorter lived. [ 12 ]


Cannabis concentrate is also commonly used in e-cigarette style vaporizer pens in the form of liquid containers known as cartridges. A  battery  connected to the  atomizer  is used to heat the cannabis oil, creating a vapor that is inhaled by the user. Cartridges typically contain different preparations of cannabis oil mixed with  cannabinoids ,  terpenes ,  solvents  (primarily  Propylene glycol  and  Glycerol ) used for thinning,  fatty acids , and  flavonoids . Natural or artificial terpenes are frequently added by manufacturers to enhance flavor, often using blends that mimic popular  cannabis strains  or sugary foods such as candy or  pastries . [ 13 ]


Of the studies that have investigated cannabis vaporization, few have addressed the quality of the vapor extracted and delivered; instead, studies usually focus on the mode of usage of the vaporizers. However, those that have addressed vapor quality have demonstrated promising results. Such studies suggest that the absence of combustion results in an aerosol that contains significantly lower amounts of harmful substances found in smoke, such as  tar ,  carbon monoxide , and carcinogenic compounds known as  polynuclear aromatic hydrocarbons  (PAH). [ 14 ] [ 9 ] [ 15 ]  One study found that cannabis smoke contains 111 compounds (including several carcinogenic PAHs) in addition to the cannabinoids, whereas only 3 additional compounds were identified in cannabis vapor, other than the cannabinoids. [ 9 ]  This suggests that the vaporization of cannabis may be a safer alternative to combusted cannabis. [ 16 ]  On the other hand, a study in the UK (where cannabis is illegal) found that some illicitly distributed cannabis vaporizers contained harmful levels of  xylazine , an animal  sedative  which can lead to overdose. [ 17 ]


An electronic cigarette is a handheld  battery -powered vaporizer that simulates  smoking  by providing some of the behavioral aspects of smoking, including the hand-to-mouth action of smoking, but without  combusting  tobacco. [ 18 ]  Using an e-cigarette is known as "vaping" and the user is referred to as a "vaper." [ 19 ]  Instead of  cigarette smoke , the user inhales an  aerosol , commonly called  vapor . [ 20 ]  E-cigarettes typically have a  heating element  that atomizes a  liquid solution  called  e-liquid . [ 21 ]  E-cigarettes may be automatically activated by taking a puff; [ 22 ]  others turn on manually by pressing a button. [ 19 ]  Some e-cigarettes look like  traditional cigarettes , [ 23 ]  but they come in many variations. [ 19 ]  Most versions are reusable, though some are disposable. [ 24 ]  There are first-generation, [ 25 ]  second-generation, [ 26 ]  third-generation, [ 27 ]  and fourth-generation devices. [ 28 ]  E-liquids usually contain  propylene glycol ,  glycerin ,  nicotine ,  flavorings , additives, and differing amounts of contaminants. [ 29 ]   E-liquids are also sold without propylene glycol, [ 30 ]  nicotine, [ 31 ]  or flavors.  [ 32 ]


The benefits and the  health risks of e-cigarettes  are uncertain. [ 33 ] [ 34 ] [ 35 ]  There is tentative evidence they may help people quit smoking, [ 36 ]  although they have not been proven to be more effective than  smoking cessation  medicine. [ 37 ]  There is concern with the possibility that non-smokers and children may start nicotine use with e-cigarettes at a rate higher than anticipated than if they were never created. [ 38 ]  Following the possibility of  nicotine addiction  from e-cigarette use, there is concern children may start smoking cigarettes. [ 38 ]  Youth who use e-cigarettes are more likely to go on to smoke cigarettes. [ 39 ] [ 40 ]  Their part in  tobacco harm reduction  is unclear, [ 41 ]  while another review found they appear to have the potential to lower tobacco-related death and disease. [ 42 ]  Regulated US  Food and Drug Administration   nicotine replacement products  may be safer than e-cigarettes, [ 41 ]  but e-cigarettes are generally seen as safer than combusted  tobacco products . [ 43 ] [ 44 ]  It is estimated their safety risk to users is similar to that of  smokeless tobacco . [ 45 ]  The long-term effects of e-cigarette use are unknown. [ 46 ] [ 47 ] [ 48 ]  The risk from  serious adverse events  was reported in 2016 to be low. [ 49 ]  Less serious  adverse effects  include abdominal pain, headache, blurry vision, [ 50 ]  throat and mouth irritation, vomiting, nausea, and coughing. [ 51 ]  Nicotine itself is associated with some health harms. [ 52 ]
In 2019 and 2020, an  outbreak of severe lung illness throughout the US has been linked to the use of contaminated black market THC vape cartridges . [ 53 ]


Vaporizers can be used to inhale other recreational drugs as well. A wide variety can be consumed this way, either dissolved in e-liquid or vaporized directly. [ 54 ]  The use of e-cigarettes to inhale the  psychedelic drug   DMT  has been reported. [ 55 ]


Studies have shown that vaporizing cannabis exposes the user to lower levels of harmful substances than smoking cannabis. [ 9 ] [ 56 ] [ 57 ] [ 58 ]  These findings are important for it is estimated that 10–20% of patients with  chronic pain ,  multiple sclerosis ,  epilepsy , and  HIV / AIDS  have admitted to smoking cannabis for therapeutic purposes.  For patients, a study found that smoking cannabis sativa reduced daily pain by 34%, a statistically significant amount. [ 59 ]


In a study published in the  Journal of Psychopharmacology  in May 2008, it was stated that vaporizers were a "suitable method for the administration of THC". [ 60 ]  A 2007 study by the  University of California, San Francisco , published in the  Journal of the American Academy of Neurology , found that "there was virtually no exposure to harmful combustion products using the vaporizing device". [ 7 ]  A 2006 study performed by researchers at  Leiden University  found that vaporizers were "safe and effective  cannabinoid  delivery system(s)". The study stated that the amount of THC delivered by vaporizers were equivalent to the amount delivered by smoking. [ 58 ]  Because of those studies and other studies, vaporizers are considered medically sound devices for delivering THC. [ 14 ]


The proposed factors affecting output include: [ 9 ] [ 58 ]


Not all those have been scientifically tested. Research using vaporizers found the delivery efficiency highest at around 226 °C (439 °F), falling to about half efficiency at 150 to 180 °C (302 to 356 °F) depending on material. [ 58 ]  The purest preparations produced the highest efficiencies, about 56% for pure THC versus 29% for plant material (female flower tops) with 12%  THCA  content. Besides THC, several other cannabinoids as well as a range of other plant components including terpenoids were detected in the plant material. Using pure THC in the vaporizer, no degradation products (delta-8-THC (D8-THC), cannabinol (CBN), or unknown compounds) were detected by  HPLC  analysis. [ 58 ]  The longer vapor is stored, the more THC is lost as it condenses on the surface of the vaporizer or the balloon. This loss may be negligible over a few minutes but may exceed 50% after 90 minutes. [ 58 ]  The Leiden University study found that as much as 30–40% of inhaled THC was not absorbed by the lungs but simply exhaled. However, they did not find large individual differences in the amounts exhaled. [ 58 ]


Vaporizers are sometimes used by chefs as a method of applying controlled heat to herbs and spices to release flavors that are otherwise difficult to titrate or apply, or that might be spoiled by overheating during cooking. [ 61 ] [ 62 ] [ 63 ]  Grant Achatz, chef-proprietor of  Alinea  in Chicago, "uses the aroma-filled bags as place-mats, punctured when plates are placed in front of the customer". [ 61 ]


A  vesosome  is a multi-compartmental structure of  lipidic  nature used to deliver  drugs . They can be considered  multivesicular vesicles  ( MVV ) [ 1 ] [ 2 ] [ 3 ] [ 4 ]  and are, therefore,  liposome -derived structures.


Vesosomes consist of one or more  bilayers  enclosing an aqueous core that contains  unilamellar   vesicles  that function as internal compartments which contain the drug and which can vary in composition from each other.
The external bilayer defines the  lumen , limits emission of the vesicle contents, and protects the vesicle contents from degradation due to  lipolytic   enzymes .
Its unique properties enable localized  drug delivery  to specific parts of the body and extend the duration of drug effect. Vesosomes are relatively straightforward to produce and they offer the flexibility to deliver multiple drugs within a single carrier, which has been shown to confer important advantages in  chemotherapy .
Internal vesicle  diameters  range from 20-500 nm and vesosome diameters range from about 0.1  micron  to more than 1.0 micron. [ 5 ]


Shortly after the first description of  liposomes , by British haematologist  Alec D Bangham  in 1961 (published 1964), at the  Babraham Institute , in Cambridge, scientists first started to contemplate the possibility of employing them as transportation systems in the  blood  stream. Since then, there have been many advances in this area, and as of 2008 there were 11 clinically approved liposomal drugs targeting a variety of pathological conditions and illnesses, including  fungal infections ,  hepatitis A ,  influenza  and certain  cancers . Now, scientists plan to take full advantage of the 40 years of progress in liposome development to enhance this transportation system by employing vesosomes.


Vesosome multicompartment structure encapsulates unilamellar liposomes within a second bilayer. For this purpose, it is necessary to form bilayers that can be opened and closed at will, without disrupting the inner content. This is achieved by adding  ethanol  to a variety of  saturated   phospholipids  in the gel phase, which drives interdigitation of phospholipids bilayers and subsequent fusion of small  vesicles  to form flat bilayer sheets. These are steady to removal of the residual ethanol until heated above the  lipid  chain  melting temperature  (T m ). The bilayers become flexible, and the sheets spontaneously close on themselves to form unilamellar vesicles. During the closure, the sheets can entrap whatever is around in suspension. By adding the vesicles aggregates including drug-loaded vesicles to the pelleted sheets before heating the mixture, encapsulation is carried out to form vesosomes.


Vesosome structure has taken advantage of the progress in liposome development as  steric stabilization ,  pH  loading of drugs (it is loaded by pH gradient), and intrinsic biocompatibility (it can be modified with a variety of agents, for example to specifically target a disease site, or promote adhesion or fusion).


A wide of molecular structures can be encapsulated in vesosomal vesicles, such as proteins with complex three-dimensional structures or condensed  DNA . The most common use is to fill the vesosome’s vesicles with certain  drugs  that are going to be delivered in a particular area.
Due to the small size of the vesosome and its good protection of the inner vesicles, it can be used in various cases, doing different functions.


If suitable receptors are included in the outer lipid bilayer of vesosomes during their preparation, then they are able to locate to inflamed areas. Once in the inflamed area, such vesosomes will deliver an  anti-inflammatory  substance from its vesicles though a  pH  gradient. Vesosomes that localise to  tumours  have also been demonstrated.
They can be used to create, in a positioned area, a different nano- environment  (considering that vesosome size is about 50 - 200 nanometres) either by altering the pH or the concentration of a particular substance.


Zydis  is a technology used to manufacture  orally disintegrating tablets  developed by  R.P. Scherer Corporation . Zydis tablets dissolve in the mouth within 3  seconds . [ 1 ]


Zydis technology was developed by  R.P. Scherer Corporation  (currently owned by  Catalent Pharma Solutions ) in 1986. [ 2 ]  The technology's first commercial application was in August, 1993, when a new dosage form of Pepcidine ( famotidine ) from  Merck & Co.  was launched in  Sweden . [ 3 ]


In November 1993 Imodium Lingual ( loperamide ) from  Janssen Pharmaceutica  was released in  Germany  with Zydis technology. [ 4 ]


In December, 1996, the  Food and Drug Administration  approved Claritin ( loratadine ) RediTabs from  Schering-Plough , the first prescription drug with Zydis technology sold in the U.S. [ 5 ]


A Zydis tablet is produced by lyophilizing or  freeze-drying  the
drug in a matrix usually consisting of  gelatin . The resulting product is very lightweight and fragile, and must be dispensed in a special blister pack.


Amipara et al., in their article "Oral disintirating tablet of antihypertensive drug" explain the technology's limitations:


The Zydis formulations consist of a drug physically trapped in a water-soluble matrix (saccharine mixture and polymer), which is freeze dried to produce a product that dissolves rapidly when placed in mouth. The ideal candidate for Zydis technology should be chemically stable and insoluble and particle size preferably less than 50  micron .


Water soluble drugs might form  eutectic mixtures  and not freeze adequately, so dose is limited to 60 mg and the maximum drug limit is 400 mg for water insoluble drug as large particle sizes might present sedimentation problems during manufacture. [ 6 ]


Zydis tablets:


Disadvantages include:


Data from "Fast Disintegrating Drug Delivery Systems: A Review with Special Emphasis on Fast Disintegrating Tablets" (2013). [ 11 ]


Meir Bialer  (born January 30, 1948) is an Israeli pharmacologist who is a David H. Eisenberg Emeritus (active) Professor of Pharmacy at the School of Pharmacy, Faculty of Medicine, of The  Hebrew University of Jerusalem  in Israel.


Bialer was born in  Petach Tikva , Israel, to a Jewish family. He completed his service in the  Israeli Army  in 1971-73. [ citation needed ]


He received his  B.Sc.  Pharm in Pharmacy in 1969, his  M.Sc.  in  Medicinal Chemistry  from  The Hebrew University of Jerusalem  in 1971, his  MBA  in 1976 and his  PhD  in Medicinal Chemistry from the same university in 1977, with a dissertation on "Antiviral Structure-Activity Relationship of Distamycin and its Derivatives." [ citation needed ]


After post-doctoral studies at the  University of Florida  (1977–79) and  University of Kentucky  (1979–80), he became a Lecturer (1980–84) and then Senior Lecturer (1984–88) and then Associate Professor (1988–93) at the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem. In 1993 he became a Full Professor at the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem. Currently, he is serving as a David H. Eisenberg Emeritus (active) Professor at the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem. [ 1 ]


Bialer was president of the Israel League Against  Epilepsy , a branch of the  International League Against Epilepsy  (ILAE), from 1996 to 2001, and as the chair of ILAE-Europe from 2009 to 2017. [ 2 ]  He also served as president of Israel Society of Clinical Pharmacy and Biopharmaceutics (ISCPB), a member of the European Society of Pharmaceutical Sciences (EUFEPS) (1991–2001).


Bialer’s research interests include:


In these areas, he has 264 peer-reviewed publications, and is an author of 16 book chapters. Since 1981 he has supervised 22 MSc students and 31 PhD students.


Meir married Shoshana Novak in 1970. They have two children Michal Bialer-Mor Yosef and Oded Bialer, as well as five grandchildren: Adi, Omri and Roni Bialer and Adam and Eitan Mor Yosef.


Gëzim Boçari  (born 25 March 1949) is an  Albanian  professor of pharmacology and a politician.


Gëzim Boçari is head of the pharmacology sector of the medicine faculty at the  University of Tirana . [ 1 ]  He is one of the writers of medicine and pharmacology textbooks of Albanian universities. [ 2 ]  In the 2009 parliamentary elections for Albania he was the head candidate of the coalition of the Pole of Freedom ( Albanian :  Poli i Lirisë ) in the district of  Vlorë .


Oana Caruana Pulpan  (born 17 April 1978) is a Maltese  chess  player. [ 1 ] [ 2 ] [ 3 ]  She was awarded the  Woman FIDE Master  title in 2009. [ 4 ]  She is a member of the  Maltese Women's National Team . Her father introduced her to chess when she was very young and has been playing it since. [ 5 ]


She is sponsored by the company she works with,  Actavis . [ 5 ]  She is also a  pharmacologist . [ 6 ]  She teaches chess classes at St. Catherine's High School in  Pembroke, Malta . [ 7 ]


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Karel Chodounský  (Latinized as  Carolus Josephus Petrus Chodounsky ; 18 May 1843 – 12 May 1931) was a Czech physician, pharmacologist and promoter of mountaineering. He was the founding professor at the institute of pharmacology at  Masaryk University . He is known as the author of the first Czech pharmacology textbook called  Farmakologie , printed in 1905. [ 1 ]


Chodounský was born in Studénka (today part of  Bakov nad Jizerou ) to estate administrator Petr and Julia née Svobodová. He studied medicine at the  University of Prague  in 1868, also spending time in the natural history museum. He worked as an assistant in physiology under  Jan Evangelista Purkyně . He worked as a physician, practising privately until 1895 and in 1884 he became an assistant professor of  balneotherapy . He habilitated in pharmacology and toxicology in 1888 and became an associate professor in 1895. He headed the institute of pharmacology at Prague and received a doctorate in 1900 and became a full professor of pharmacology in 1902. Chodounský demonstrated by experiments that he conducted on himself that infectious colds had nothing to do with low temperatures. He wrote about this in his 1907 book  Erkältung und Erkältungskrankheiten . In 1919 he was involved in establishing pharmacology at the Masaryk University, Brno, and served there until 1923. [ 2 ]


Chodounský was a champion skater and took a keen interest in mountaineering. He was involved in the establishment of the Slovenian Alpine Society in Prague in 1897, serving as its president until 1914. He promoted the training of alpine guides, the opening of trails, and the publication of books on mountaineering. In 1901 he founded a society to support Slovenian students in Prague. He edited the Czech medical periodical  Časopis lékařů českých  (1878–1888) and for his contributions he received a Knight's Cross of Emperor Franz Joseph. He was also awarded an honorary doctorate in 1929 by Masaryk University. [ 2 ] [ 1 ]


He died on 12 May 1931 in  Prague , aged 87. [ 1 ]


His daughter Marie Chodounská (d. 1922) became an artist. [ 3 ]


Ferdinand Giese  ( Johann Emanuel Ferdinand Giese ; 13 January 1781 – 22 May 1821) was a  Baltic German  pharmacologist. 1817–1818 he was the  rector of Tartu University . [ 1 ]


He graduated from  Erfurt University . 1804–1814 he worked at  Kharkiv University . Since 1814 he taught at  Tartu University . [ 1 ]


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Sabine Hadida  is a pharmacologist and senior vice president at Vertex Pharmaceuticals. She works at Vertex's cystic fibrosis research center in San Diego. She was awarded the  Breakthrough Prize in Life Sciences  in 2024.


Hadida has a bachelor's degree, master's degree, and Ph.D. in pharmacy from the  University of Barcelona , Spain. [ 1 ]  She worked as a postdoctoral fellow at the  University of Pittsburgh  studying fluorous chemistry. [ 1 ]


At Vertex Pharmaceuticals, Hadida led the chemistry team to work on drug treatments for  cystic fibrosis  and pain. [ 1 ]


Hadida has garnered over 30 peer reviewed scientific articles and over 60 U.S. patents. [ 1 ]  She is the recipient of the 2022 Drug Hunter Award, 2019 Distinguished Scientist Award by the American Chemistry Society, San Diego Chapter, and the 2013 American Chemistry Society Heroes of Chemistry award. [ 1 ] [ 2 ]


In September 2023, she received the 2024 Breakthrough Prize in Life Sciences alongside Paul Negulescu and Frederick Van Goor, for developing treatment for cystic fibrosis. [ 3 ]


James Alan Shayman  is an American  physician scientist ,  nephrologist , and  pharmacologist . He is Professor of Internal Medicine and Pharmacology and the Agnes C. And Frank D. McKay Professor at the  Medical School of the University of Michigan . [ 1 ]  He also serves as a staff nephrologist at the Ann Arbor Veterans Administration Medical Center. [ 2 ]


Shayman's research interests span the study of  lysosomal  biology and related disorders. His group is most known for the development of  small-molecule  inhibitors of  glycosphingolipid  synthesis and their use in lysosomal glycosphingolipid storage disorders. His team also discovered and characterized a novel lysosomal  phospholipase A2 , PLA2G15 and is investigating its role in  phospholipidosis . He has published over 160 articles. [ 3 ]


Shayman is a Fellow of the  American Heart Association  and  American Society of Nephrology  as well as a Life Fellow of  Clare Hall at the University of Cambridge . He has served as an Associate Editor for the  Journal of Clinical Investigation  and  Translational Research  and is serving in the same role for the  Journal of the American Society of Nephrology . [ 4 ]


Shayman obtained a Bachelor of Arts degree from  Cornell University  in 1976, and received an M.D. in 1980 from  Washington University in St. Louis . From July 1980 to June 1983, he served as a house officer in Medicine at  Barnes Hospital  in  St. Louis , Missouri. Beginning in 1983, he pursued a Postdoctoral Fellowship with a specialization in Nephrology and Pharmacology under the mentorship of Aubrey Morrison and  Oliver H. Lowry  at Washington University School of Medicine in St. Louis. [ 5 ]


Following his post-doctoral fellowship training, in 1985, Shayman began his academic career as an instructor in the Renal department of Washington University School of Medicine. He was recruited to the  University of Michigan  where from 1986 to 1992 he was appointed as assistant professor in the Department of Internal Medicine, Division of Nephrology. He subsequently was promoted to the positions of associate professor in 1992 and professor in 1997, respectively with a secondary appointment in Pharmacology. He has been serving as the Agnes C. and Frank D. McKay Professor. [ 1 ]


Shayman was the Associate Chair for Research Programs at the Department of Internal Medicine and Associate Vice President for Research in Health Sciences of the University of Michigan. [ 6 ]  In addition, he has been serving as a staff nephrologist Veterans Administration Medical Center in Michigan. [ 2 ]


Shayman's research is focused on lysosomal biology, the  pathophysiology  of traditional  lysosomal storage disorders , and the role of the lysosome in more prevalent diseases including  diabetes  mellitus and  polycystic kidney disease . A particular emphasis has been on the development of  drug therapeutics  for disorders of glycosphingolipid metabolism. This work has resulted in several patents including "Amino ceramide-like compounds and therapeutic methods of use" [ 7 ]  and "Pyridine inhibitors of glucosylceramide synthase and therapeutic methods using the same." [ 8 ]


An early collaboration with Norman Radin focused on substrate reduction as an alternative to enzyme replacement therapy for the treatment of lysosomal disorders such as Gaucher disease. It was suggested that substrate reduction posits that inhibition of metabolites that accumulate in the lysosome due to the loss of activity of a specific hydrolase can be treated with reversible inhibitors of specific anabolic enzymes. Following an early collaboration with Radin, the Shayman group went on to develop inhibitors of glucosylceramide synthase followed by proof of concept studies in models of Gaucher and Fabry disease that experimentally established the viability substrate reduction therapy. [ 9 ] [ 10 ]  Although this concept was initially met with skepticism from the academic and pharmaceutical communities, these compounds were eventually licensed to the Genzyme Corporation for clinical development in 2000. In 2014 eliglustat tartrate was approved by the Food and Drug Administration and the European Medicines Association. Eliglustat tartrate was the first orally bioavailable agent approved as the first stand-alone substrate reduction therapy for Gaucher disease type 1. [ 11 ] [ 12 ]


Shayman's work on developing the "first in class" glycosphingolipid synthesis inhibitor led to the consideration of whether more common disorders might be amenable to targeting glucosylceramide synthase. [ 13 ]  Based on fundamental studies by his group and others demonstrating a role for glucosylceramide metabolism in conditions associated with aerobic glycolysis, [ 14 ]  including diabetes [ 15 ]  and polycystic kidney disease, glucosylceramide synthase inhibitors have been the focus of preclinical and clinical studies evaluating the potential for extended use applications of eliglustat and related compounds. [ 16 ]


In collaboration with Scott D. Larsen, Shayman's work has also been directed toward the identification of brain-penetrant glycolipid synthesis inhibitors for the treatment of Gaucher disease types 2 and 3, [ 17 ]  GM2 gangliosidoses including Tay-Sachs and Sandhoff disease, and GM1 gangliosidosis. [ 18 ]  Using computational analysis comparing eliglustat to known CNS penetrant compounds, novel glucosylceramide synthase inhibitors were designed around the eliglustat pharmacophore, demonstrating the lower glucosylceramide and ganglioside levels within the brain. [ 19 ]


The Shayman group has worked on the elucidation of the mechanisms underlying the vasculopathy of Fabry disease. His initial work led to the identification of three inducible models of vascular disease in the alpha-galactosidase A knockout mouse. [ 20 ]  These models included oxidant-induced arterial thrombosis, accelerated atherogenesis, and impaired arterial relaxation. Both decreased nitric oxide bioavailability [ 21 ]  and endothelial nitric oxide synthase uncoupling have been demonstrated to underlie these abnormalities. The insights led to identifying 3-nitrotyrosine as a biomarker for endothelial dysfunction in both experimental models and patients affected by classic forms of Fabry disease. [ 22 ] [ 23 ]


Attempts to delineate potential off-target effects of eliglustat led to the discovery of a novel lysosomal hydrolase, phospholipase A2 group XV (PLA2GXV). This enzyme was initially identified as a transacylase and named 1-O-acylceramide synthase. [ 24 ]  PLA2GXV is 50 percent identical to LCAT. In collaboration with John Tesmer and colleagues, the structure of PLA2GXV and, by extension, of lecithin cholesterol acyltransferase (LCAT) were solved. Mice engineered to be deficient in PLA2GXV developed a pulmonary phenotype associated with the conversion of alveolar macrophages to foam cells, a phenotype that resembles amiodarone toxicity. [ 25 ]  A 2021 work has also identified PLA2GXV as the site of action for many drugs that cause a form of toxicity termed phospholipidosis. [ 26 ]


Hedwig Langecker  (29 January 1894 – 31 January 1989) was a Bohemian, Czech, and German pharmacologist known for her discovery of the pharmacological properties of  Polygonatum officinale  and  Polygonatum multiflorum . She was also known for her studies of steroid hormone biochemistry and her prolific output, which included over 200 scientific articles and several textbooks. Her career began at the  German University in Prague , where she earned her M.D. in 1920 and a Ph.D. in 1923, and was  habilitated  in 1926; Langecker then became a professor and served in that role until 1945. That year, she moved to the  Free University of Berlin , where she was a professor until 1959 and an emerita professor until her death in 1989. [ 1 ]


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Dr. Henry Isaac Clore Lowe   OJ   OD  (born April 9, 1939) is a Jamaican scientist, philanthropist and businessperson. His career began in academia where he worked at  College of Art, Science, and Technology  (CAST) for 16 years, before entering public life by joining the Ministry of Energy. He now owns and manages a variety of businesses in the health industry.


Henry Lowe was born on April 9, 1939, in St. Andrew, Jamaica. His family was "far from being wealthy" and were devout Catholics. His father David was a Cabinet Member and his mother Josephine was a part-time tailor and a homemaker. [ 1 ]  Lowe was the fourth of ten children. [ 2 ]  At four years old Lowe was enrolled at the Woods' infant school. Though it was located on Metcalfe Road, a neighborhood which was considered affluent at the time, his school hosted its classes in sheds behind a house.  Lowe attended primary school in  Port Maria  and later attended  Excelsior High School . [ 3 ]


Lowe was accepted into the  University of the West Indies  in 1959 with scholarship, [ 4 ]  where he graduated with a bachelor of Science and Honours degrees in natural science. Lowe obtained a Master's in Pharmaceutical and Medicinal chemistry from the  University of Sydney [ 5 ]  and his Ph.D. at  Manchester University . [ 6 ]  To both universities Lowe was awarded a  British commonwealth scholarship  becoming "the first Jamaican, and maybe the only one ever, to be awarded two commonwealth Scholarships". [ 7 ]  He pursued post-doctoral studies at the  Bolton Institute of Technology , the  Massachusetts Institute of Technology  and  Harvard University . [ 8 ]


The year after graduating from Excelsior high school Lowe was himself hired as a science teacher at Holmwood high school. [ 9 ]  After graduating from the University of the West Indies, he taught chemistry at Excelsior high school and was appointed the head of the Science Department for one year, after which he began lecturing at CAST on September 10, 1964. [ 10 ]  His time at this institution was interrupted intermittently by educational pursuits. Lowe returned to the College of Art Science and technology in 1970 and was made the head of the science department in 1973 – the first native Jamaican to have held this position. [ 11 ]  Lowe returned again where he was made vice principal of academic affairs. [ 12 ]  Being persuaded by Jamaica's then Ambassador to the U.S., Douglas Fletcher, Lowe left his position at CAST to join the Ministry of Energy to help manage the severe energy crisis Jamaica was experiencing. [ 13 ]


Lowe's research is focused on ascertaining medicinal and pharmacological qualities of  Jamaican plants; in particular  Cannabis  and  Tillandsia recurvata . Lowe has been involved in Cannabis research "since 1972". [ 14 ]  His Ph.D. focused on examining "the structure activity relationships of some of the cannabinoids in ganja". [ 15 ]  Lowe, in collaboration with various colleagues has produced experimental findings which demonstrate the efficacy of cannabis flavonoids in combating illnesses such as  hepatitis c . [ 16 ] [ 17 ] [ 18 ]  Lowe's interest in  Tillandsia recurvata  began during his doctoral studies. [ 6 ]  Lowe and his research team have since shown that it can be potent medicine for prostate cancer through its  cytotoxic  properties towards cancer cell lines (P-3C and P-45). [ 19 ]  Lowe produces a variety of health products based on his discoveries in these areas. [ 20 ]


Lowe developed the first National Energy Policy and Management plan for Jamaica as the director of its Ministry of Energy. It included  an agreement with  Venezuela  that 25% of the revenue generated from Jamaica's purchase of Venezuelan oil would be re-directed towards various Jamaican development projects. Lowe also achieved  the reduction of Jamaica's use of oil by 20 percent. [ 21 ]  After this, Lowe helped establish the Ministry of Science, Technology and the Environment, before joining the Ministry of Agriculture, [ 22 ]  and then the Ministry of Public Utilities and Transport. [ 23 ]


Lowe had been a consultant for Blue Cross of Jamaica since the 1970s, and was appointed to the board of trustees in 1988. Following the resignation of then CEO Hylton McIntosh, Lowe was appointed as CEO in 1990. [ 24 ]  Lowe would later acquire the majority of the Blue Cross of Jamaica from its previous holder, the  Blue Cross Blue Shield Association . Lowe sold his shares in 2008 to  Sagicor . [ 25 ]


In 2000 Lowe purchased a two-acre property on 39 Lady Musgrave road. Lowe used this land to create the "Eden gardens wellness center and spa" – a business venture which also aligns with his ideals of promoting wellness and health in Jamaica. [ 26 ]  More property was purchased across from 44 lady Musgrave road which was being used for an expansion as of 2012. Novlet green took over management of the facility in 2006. [ 27 ]


In 2007 at a conference of the Caribbean poison information network (CARPIN), Lowe spoke of the commercial benefits possible from research into medicinal  cannabis . [ 28 ]   In 2013 Lowe established Medicanja; a company to produce  and commercialize  products based on cannabis. [ 29 ] [ 30 ] [ 31 ]  He is the firm's  Executive Chairman and chief scientist. [ 32 ] [ 33 ]  Medicanja has a research facility at the University of the West Indies. [ 34 ]  On July 26, 2018, Medicanja released twelve nutraceutical products. Six of these products; CanjaRub, CanjaCol, Relevium Cream, Relevium Spray, Somnican (One Drop) Orals, and Tivasat, are designed to inhibit pain. Six others are intended for specific usage: CBD Oil Sublingual Drops designed to reduce nausea, I-Cann designed for those with glaucoma and intra-ocular pressure, Epilec Pro for epilepsy, Sclorican for pain and discomfort caused by  multiple sclerosis , Cannrepel a mosquito repellent; and the "Oromuccosol Spray". All of these products have been approved by the  FDA . [ 35 ] [ 36 ]  On December 3, 2018, the Development Bank of Jamaica   agreed to provide Medicanja with $7 million to facilitate the clinical trials of its experimental drug, "Drug X Version 2". [ 37 ]  The firm developed drug, Chrysoeriol, which could be used to treat  acute myeloid leukaemia.  On July 12, 2017, Lowe announced Chrysoeriol had been given orphan drug status by the FDA [ 38 ] [ 39 ] [ 40 ]  Lowe,  working with various academics, has filed for sixteen patents in the  United States , six of which have been granted. [ 41 ]


In 1992 Lowe founded the "Environmental Health Foundation", a non-governmental charitable organization which identifies, implements and gives grants to pro-social projects. in "health, education, environment, science & technology and the development of knowledge". [ 42 ]  In 2015, the EHF won an  Energy Globe award  for its three-year program (2011-2014) designed to increase the resilience of Jamaican farmers to climate change, in partnership with the  United States Agency for International Development  from which it received funding. As of 2018, Lowe was the charity's executive chairman. [ 43 ]


Collen Masimirembwa  (born 1967) is a biomedical pharmacologist from  Zimbabwe . He is a  Distinguished Professor  of  Clinical Pharmacology  at the  University of Witswatersrand , [ 1 ]  and serves as the president and chief scientific officer at the African Institute of Biomedical Science and Technology (AiBST). His research in Africa has contributed to the field of pharmacogenetics, particularly in understanding the genetic diversity and drug response of African populations. In 2018, he was awarded the HUGO Africa Award. [ 2 ]  He is a fellow of the Calestous Juma Leadership Fellowship, [ 3 ]  African Academy of Sciences (AAS) and the Zimbabwe Academy of Sciences (ZAS).


He has authored over 100 papers in peer-reviewed journals and book chapters and has guided numerous postgraduate students and postdoctoral fellows. [ 4 ]


Masimirembwa was born in 1967 in Zimbabwe [ 5 ]  and received his BSc (Hons) and DPhil degrees in biochemistry from the University of Zimbabwe in 1993. [ 6 ]  Fascinated by the then-emerging field of pharmacogenetics, he conducted studies at the Karolinska Institute in Sweden in 1995, [ 5 ]  where he earned his PhD in Medical Biochemistry and Biophysics. His doctoral research was centered on the molecular mechanisms of drug metabolism and toxicity. [ 7 ] [ 8 ]


After obtaining his PhD, Masimirembwa returned to the University of Zimbabwe and served as a senior lecturer and head of the Department of Biochemistry from 1992 to 1997. [ 6 ]  He later joined AstraZeneca R&D in Sweden as a principal scientist and project leader, focusing on drug discovery and development in various areas such as cardiovascular, gastrointestinal, and infectious diseases. He played a key role in establishing the AstraZeneca Africa Pharmacogenetics Research Network, which aimed to study the genetic diversity and drug response of African populations. [ 7 ] [ 6 ]


Later in 2008, Masimirembwa founded and assumed the position of president and chief scientific officer at the African Institute of Biomedical Science and Technology (AiBST), a non-profit research institute in Zimbabwe that focuses on biomedical science and technology, with an emphasis on pharmacogenetics and clinical pharmacology. [ 9 ]


At the institute, he manages collaborations with various academic, industry, and government partners. He also leads the African Pharmacogenomics Consortium (APC), a network that aims to advance pharmacogenomics research and applications in Africa. [ 6 ]  He is also a distinguished professor of health sciences research at the University of the Witwatersrand (South Africa).  [ 7 ] [ 10 ]


Masimirembwa is a fellow of the Zimbabwe Academy of Sciences (ZAS) [ 5 ]  and the African Academy of Sciences (AAS) among many other honors .  In November 2021, Masimirembwa was selected as a Calestous Juma Science Leadership Fellow by the Bill and Melinda Gates Foundation, to develop a research and innovation ecosystem, train scientists, and create centres of excellence in genomic medicine research to enhance Africa’s sustainable development in genomic and pharmaceutical capabilities. [ 11 ]


Collen Masimirembwa was named a Fellow of the  Zimbabwe Academy of Sciences  in 2017 and the  African Academy of Sciences  in 2018. In 2018, he was awarded the  HUGO Africa  Award. [ 12 ]  The Grand Challenges Africa Award was presented to him in 2016. He was the recipient of the  EDCTP Senior Fellowship  Award in 2014 [ 13 ]  and the  Wellcome Trust  Senior Fellowship Award in 2012.  AstraZeneca R&D  acknowledged his work with the Global Scientific Award in 2006 and the Global Innovation Award in 2005. [ 7 ] [ 11 ]  Additionally, he received the Calestous Juma Leadership Fellowship in 2021 [ 14 ]  and the PMCW 2025 Pioneer Award. [ 15 ]


Viness Pillay  FAAS  (1970–2020) was a South African professor of  pharmacy  at the  University of the Witwatersrand  in  Johannesburg . [ 1 ] [ 2 ]  He was the Director of the Wits Advanced Drug Delivery Platform (WADDP), a member of  African Academy of Sciences , Academy of Translational Medicine Professionals (ATMP) and a beneficiary of the 2013  Olusegun Obasanjo  Innovative Award for developing the RapiDiss Wafer Technology as an innovative way to provide effective  anti-retroviral  (ARV) drug therapy to children afflicted with  HIV/AIDS . [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]


He obtained his master's degree in pharmacy from the  University of Durban-Westville  (South Africa) in 1996 and bagged his PhD at  Temple University  in 2000 as a Fulbright Scholar. [ 6 ]


He developed RapiDiss Wafer Technology as an innovative way to provide effective anti-retroviral (ARV) drug therapy to children afflicted with HIV/AIDS. He developed the world's fastest dissolving matrix for the onset of rapid drug action in the human body, a neural device for therapeutic intervention in spinal cord injury and novel wound healing technologies. He also came up with his own molecular modelling paradigms called PEiGOR Theory - Pillay's Electro-influenced Geometrical Organization-Reorganization. This theory was published in the International Journal of Pharmaceutics. [ 6 ] [ 7 ] [ 5 ] [ 3 ]


He was elected a Fellow of the  Academy of Science of South Africa  in 2012. He was also a member of the  American Chemical Society , the American Association of Pharmaceutical Scientists, the  New York Academy of Sciences , the Academy of Pharmaceutical Sciences of South Africa, and The Biomaterials Network. [ 6 ]


He was a beneficiary of National Research Foundation (NRF) Awards. [ 8 ]


Pillay died on 24 July 2020 after a lengthy illness. He left behind a wife and a daughter. [ 1 ] [ 2 ]


Jānis Polis  (25 June 1938 – 12 April 2011) was a  Soviet  and  Latvian   pharmacologist  and the developer of one of the first methods of synthesis of  rimantadine , which was discovered in 1963 by William W. Prichard of Du Pont & Co. [ 1 ]  He was born in  Eleja parish , Latvia. On 6 February 2009, Polis was awarded the  WIPO  Award for Outstanding Inventors. [ 2 ]  Polis died in  Riga ,  Latvia  on 12 April 2011 at the age of 72.


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Kenneth D. Tew  is a  Scottish-American   pharmacologist , academic and author. He is a professor in the Department of Cell &  Molecular Pharmacology  and the  John C. West  Endowed Chair in  Cancer Research  at the  Medical University of South Carolina . [ 1 ]


Tew's research primarily focuses on identifying cancer strategies with strong translational potential, particularly in the context of  redox  pathways, and resistance to various drugs to understand redox mechanisms and their connections to essential signaling pathways. [ 2 ]  He has authored, co-authored and edited research articles and books such as  Preclinical and Clinical Modulation of Anticancer Drugs  and  Basic Science of Cancer . He is the recipient of the Outstanding Investigator Grant from the  National Cancer Institute  in 1993, the 2003  American Cancer Society  Scientific Research Award and the 2010 Astellas USA Foundation Award from the  American Society for Pharmacology and Experimental Therapeutics . [ 3 ]


Tew is an Elected Fellow of the  American Association for the Advancement of Science [ 4 ]  and the American Society for Pharmacology and Experimental Therapeutics. [ 5 ]  He is an Executive Editor of  Biomedicine & Pharmacotherapy . [ 6 ]


Tew earned a Bachelor of Science in  Microbiology / Genetics  from the  University of Wales, Swansea  in 1973 and a PhD in Biochemical  Pharmacology  from the  University of London , where he also received postdoctoral training in 1976. He served as the Head of the Basic Pharmacology Program at the  Lombardi Cancer Center  from 1982 to 1985, when he became a member and later Chairman of Pharmacology at the  Fox Chase Cancer Center . Concurrently, he worked as an Adjunct Associate Professor of Pharmacology at the  University of Pennsylvania  until 1990 and was awarded his DSc from the University of London in 1995. [ 7 ]


Tew was appointed the G. Willing Chair in Cancer Research at the  Medical University of South Carolina  from 1999 to 2004. He was the Director of the Developmental Cancer Therapeutics Program at Hollings Cancer Center from 2004 to 2019, and serves as a professor in the Department of Cell & Molecular Pharmacology at the Medical University of South Carolina. [ 1 ]


Tew has been the John C. West Chair in Cancer Research at the Medical University of South Carolina since 2004. [ 8 ]


Tew held the position of Associate Editor from 1993 to 2007 and later assumed the role of Senior Editor in the Experimental Therapeutics, Molecular Targets, and  Chemical Biology  Section from 2007 to 2018 for the journal  Cancer Research . Concurrently, he held editorial positions including, Editor for  Cellular Pharmacology , and Editor-in-Chief of  Journal of Pharmacology and Experimental Therapeutics . [ 7 ]


Tew has been the Editor (USA) of  Biomedicine & Pharmacotherapy  since 2002 [ 6 ]  and Serial Editor for  Advances in Cancer Research  since 2011. [ 9 ]  Additionally, he has held appointments at InVaMet Therapeutics and the  Greehey Children's Cancer Research Institute  Scientific External Advisory Board since 2019. [ 10 ]


Through his research laboratory, the Tew laboratory, he has conducted research in redox pathways, with an emphasis on  drug development ,  biomarker  identification, and comprehending the effects of  reactive oxygen  and  nitrogen species  on  cancer cells . [ 2 ] [ 11 ]  He has focused on distinct  post-translationally modified   S-glutathionylated  proteins affecting  cell-signaling  pathways, potentially acting as  surrogate plasma biomarkers  for drug response induced by  oxidative  and nitrosative stress. He holds patents for his work, contributing to the development of a  glutathione S-transferase -activated  prodrug  and two small molecules in clinical development as potential  myeloproliferative  agents. [ 12 ]


Tew has co-authored 2 books focusing on carcinogenesis and cancer treatment strategies. He co-wrote  Preclinical and Clinical Modulation of Anticancer Drugs  with Peter J. Houghton and Janet A. Houghton, providing an analysis of theoretical and practical approaches to the design and implementation of modulation principles. His collaborative work with Gary D. Kruh,  Basic Science of Cancer , explored the advancements in cancer research, covering interrelated topics such as  tumor suppressor genes ,  apoptosis ,  transcriptional regulation , pharmacology of anticancer drugs,  cytogenetic techniques ,  oncogenes , and  signal transductions . [ 13 ]


Tew co-edited books from the series  Advances in Cancer Research  alongside Paul B. Fisher, where they provided reviews on diverse cancer research topics. In a review published in the  Journal of Medicinal Chemistry , Thomas J. Bardos wrote about the series, "This rapidly growing series of volumes containing many excellent, highly informative, in-depth reviews on a variety of timely topics relating to cancer research has always been most representative in the areas of tumor biology and immunology." [ 14 ]