Hair Follicles – An Efficient Storage and Penetration Pathway for Topically Applied Substances

Lademann J., Richter H., Teichmann A., Otberg N., Blume-Peytavi U., Luengo J., Weiß B., Schaefer U.F., Lehr C., Wepf R.

The penetration and storage behavior of dye-containing nanoparticles (diameter 320 nm) into the hair follicles was investigated. The results were compared to the findings obtained with the same amount of dye in the non-particle form. In the first part of the experiments, the penetration of the dye into the hair follicles was investigated in vitro on porcine skin, which is an appropriate model for human tissue. It was found that the nanoparticles penetrate much deeper into the hair follicles than the dye in the non-particle form, if a massage had been applied. Without massage, similar results were obtained for both formulations. Subsequently, the storage behavior of both formulations in the hair follicles was analyzed in vivo on human skin by differential stripping. Using the same application protocol, the nanoparticles were stored in the hair follicles up to 10 days, while the non-particle form could be detected only up to 4 days. Taking into consideration the surface structure of the hair follicles, it was assumed that the movement of the hairs may act as a pumping mechanism pushing the nanoparticles deep into the hair follicles.

Otberg N., Teichmann A., Rasuljev U., Sinkgraven R., Sterry W., Lademann J.

<i>Aims:</i> Follicular drug delivery is the prerequisite for an effective treatment of androgenetic alopecia or other reasons of premature hair loss. <i>Methods:</i> The follicular penetration of caffeine, applied topically in a shampoo formulation for 2 min, was measured with highly sensitive surface ionization in combination with mass spectroscopy, a selective method for the detection of very small quantities of transcutaneously absorbed substances in the blood. An experimental protocol, developed to selectively block the follicular pathway within the test area, was used. Based on this principle, a clear distinction between interfollicular and follicular penetration of topically applied caffeine was feasible. <i>Results:</i> After 2 min, caffeine penetrated via the hair follicles and stratum corneum. <i>Conclusion:</i> It was found that the penetration via hair follicles was faster and higher compared with the interfollicular route and that hair follicles are the only pathway for fast caffeine absorption during the first 20 min after application.

Jung S., Otberg N., Thiede G., Richter H., Sterry W., Panzner S., Lademann J.

Liposomes had been widely used for drug delivery in the past. In this study, five different liposomes were used as a follicular delivery system in pig ear skin. The liposomes mainly differed in their sphere diameter, lipid composition, and surface charge. A novel class of liposomes being amphoteric in their charge behavior are compared to established anionic and cationic liposomes. Two different fluorescent dyes, hydrophilic carboxyfluoresceine or lipophilic curcumin, were enclosed in the liposomes and used as model drugs. The fluorescent dyes were also applied in a standard formulation for reference. The penetration depth of the dyes was measured by laser scanning microscopy in histological sections. One hour, 3, 5, and 7 days after application, biopsies were taken and the penetration depth into the hair follicle was measured in longitudinal sections. The liposomes showed a higher penetration depth compared to the standard formulation. The relative penetration depth of the dyes, applied in the standard formulation, averaged 30% of the full follicle length during the whole observation period, whereas the liposomal formulations penetrated considerably deeper into the hair follicles. Amphoteric and cationic liposomes reached an average relative penetration depth of approximately 70% of the full hair follicle length.

Vogt A., Combadiere B., Hadam S., Stieler K.M., Lademann J., Schaefer H., Autran B., Sterry W., Blume-Peytavi U.

Although conventional vaccines have generated major successes in the control of infectious diseases, several obstacles remain in their development against chronic diseases (HIV, tuberculosis), against which no current candidate vaccines yet ensure protection. The transcutaneous route of vaccine administration appears to be a promising approach of targeting vaccines toward antigen-presenting cells (APCs) and thus improving immune responses. We investigated the suitability of nanoparticles in this approach. We found a high density of Langerhans cells (LCs) around hair follicles that, when sorted, readily internalized all size particles. However, flow cytometry after transcutaneous application of 40, 750, or 1,500nm nanoparticles on human skin samples revealed that only 40nm particles entered epidermal LC. Fluorescence and laser scan microscopies, which were carried out to identify the penetration pathway of transcutaneously applied nanoparticles, revealed that only 40nm particles deeply penetrate into vellus hair openings and through the follicular epithelium. We conclude that 40nm nanoparticles, but not 750 or 1,500nm nanoparticles, may be efficiently used to transcutaneously deliver vaccine compounds via the hair follicle into cutaneous APCs.

Teichmann A., Otberg N., Jacobi U., Sterry W., Lademann J.

Investigations into the penetration pathways of topically applied substances through the skin play an important role in dermatological science. Recently, the hair follicles have increasingly been recognized as an important pathway for percutaneous penetration, although the role of the follicles has still not been clarified in detail. Therefore, the aim of the present study was to develop an in vivo method for the analysis of the follicular rate of penetration processes. In order to reach this goal, the follicles were excluded from the penetration process of topically applied substances. Different study designs were evaluated, and we were able to show that the application of nail varnish to each follicular orifice represents an effective method of blocking the follicles selectively against the penetration of topically applied substances. In dermatological science, there is new information on the physiology of skin penetration processes, thus allowing examination of the follicular rate of penetration and improvement of the pharmacokinetics of topically applied substances.

Lademann J., Richter H., Schaefer U.F., Blume-Peytavi U., Teichmann A., Otberg N., Sterry W.

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of particular substances in the range of 300–400 nm. In this regard, it was assumed that the rigid hair shaft acts as a geared pump, moving the particles deeper into the hair follicle. In the present investigation, the storage reservoir capacity of the stratum corneum and the hair follicle infundibulum and canal are compared. Interestingly, we could demonstrate a 10 times longer storage within the hair follicles. These results underscore the importance of the hair follicle for drug delivery purposes, mainly highlighting new possibilities for the future concerning retarded delivery, application frequency, and galenic design.

Vogt A., Mandt N., Lademann J., Schaefer H., Blume-Peytavi U.

The penetration of topically applied compounds varies considerably in the different regions of the human body. The presence of hair follicles significantly contributes to this effect by an increase in surface area and a disruption of the epidermal barrier towards the lower parts of the hair follicle. The human hair follicle, hereby, serves not only as a reservoir, but also as a major entry point for topically applied compounds. Topical delivery of active compounds to specific targets within the skin may help reduce side-effects caused by unspecific reactions, and may help develop new strategies in the prevention and treatment of skin diseases. Various drug carrier and drug delivery systems are currently being investigated. The aim of these investigational efforts is to direct topically applied compounds to the different types of hair follicles and, ideally, to specific compartments and cell populations within the hair follicles. Follicular targeting offers opportunities for new developments, not only in hair therapy and in the treatment of hair follicle associated diseases but also in gene therapy and immunotherapy.

Toll R., Jacobi U., Richter H., Lademann J., Schaefer H., Blume-Peytavi U.

The transfollicular administration of pharmacologically active molecules is of current therapeutic interest, mainly with regard to delivery to specific sites of the hair follicle (HF) and the reduction of hepatic metabolism and systemic toxicity. HF are privileged pathways for specific molecules depending on formulations, which enter faster into these shunts than through the stratum corneum. The aim was to optimize the delivery of fluorescent microspheres into the HF, thereby, developing a standardized protocol for follicular targeting with microspheres. The number of HF showing penetration, as well as the depth of penetration, was determined. Freshly excised skin samples with terminal HF were divided into groups, with or without prior treatment with cyanoacrylate skin surface stripping-technique (CSSS). Thereafter microspheres at a size of 0.75-6.0 microm were applied according to the developed standardized protocol. Skin biopsies were obtained, shock-frozen, and sectioned in 5 microm slices. We demonstrated a selective penetration route of the microspheres into the HF. Optimal microsphere size proved to be approximately 1.5 microm, with a 55% rate of all HF, and with a maximum penetration depth of >2300 microm. Without previous CSSS treatment of the skin, the transfollicular microsphere penetration was below 27% with a maximum penetration depth of 1000 microm. Thus, the basis for follicular targeting of essential structures containing stem cells for keratinocytes, melanocytes, and mast cells has been laid.

Otberg N., Richter H., Schaefer H., Blume-Peytavi U., Sterry W., Lademann J.

For the evaluation and quantification of follicular penetration processes, the knowledge of variations of hair follicle parameters in different body sites is basic. Characteristics of follicle sizes and potential follicular reservoir were determined in cyanoacrylate skin surface biopsies, taken from seven different skin areas (lateral forehead, back, thorax, upper arm, forearm, thigh, and calf region). The highest hair follicle density and percentage of follicular orifices on the skin surface and infundibular surface were found on the forehead, whereas the highest average size of the follicular orifices was measured in the calf region. The highest infundibular volume and therefore a potential follicular reservoir was calculated for the forehead and for the calf region, although the calf region showed the lowest hair follicle density. The calculated follicular volume of these two skin areas was as high as the estimated reservoir of the stratum corneum. The lowest values for every other parameter were found on the forearm. The present investigation clearly contradicts former hypothesis that the amount of appendages of the total skin surface represents not more than 0.1%. Every body region disposes its own hair follicle characteristics, which, in the future, should lead us to a differential evaluation of skin penetration processes and a completely different understanding of penetration of topically applied drugs and cosmetics.

Otberg N., Richter H., Knuttel A., Schaefer H., Sterry W., Lademann J.

Hair follicles have been assigned an increasingly significant role in dermatopharmacology. Previous studies have shown that the penetration of substances into the follicle depends on its activity. Telogen follicles that were not producing sebum were closed for follicular penetration. The present study uses optical coherence tomography (OCT) to show that the orifices of inactive follicles are blocked by plugs formed of corneocytes. The follicular penetration of a fluorescent dye was analyzed by cyanoacrylate surface biopsies in combination with laser scanning microscopy. Surface exfoliation and cyanoacrylate surface peels were used as a pre-treatment to remove the corneocyte plugs from the follicular orifices and therefore to open up closed follicles. It was shown that both procedures could increase the number of open hair follicles significantly. The present experiments show that OCT in combination with laser scanning microscopy is an excellent non-invasive in vivo method for the investigation of hair follicle properties and follicular penetration processes.

Barry B.W.

The role of hair follicles in transdermal delivery remains difficult to elucidate due partly to animal model complications. This paper explores a novel technique employing two human skin membranes to differentiate shunt route delivery from bulk transepidermal input. The method monitors penetration through epidermal membranes and compares this with delivery through a sandwich of stratum corneum and epidermis, with the corneum forming a top membrane. As orifices of shunts occupy only 0.1% of the area, there is negligible chance that shunts in the membranes will superimpose. The top layer blocks shunts available in the bottom layer. If shunts are important, delivery through sandwiches will be much reduced compared with that through epidermis, allowing for increased double membrane thickness. Experiments with penetrants under passive, iontophoretic and electroporation conditions illustrated the value of the method. A Monte Carlo simulation suggested that any failure of membrane adherence would not affect conclusions drawn.

Genina E.A., Bashkatov A.N., Sinichkin Y.P., Kochubey V.I., Lakodina N.A., Altshuler G.B., Tuchin V.V.

We present experimental results on the in vitro and in vivo study of dye diffusion into human skin and hair follicles. We have studied some commercially available dyes for potential using in the laser selective thermolysis. The degree and the depth of hair follicle dyeing inside the skin were determined. For hairs in different stages the sebaceous gland was stated as a reservoir for a dye administration. It was found that the penetration depth of dyes is about 1.2 mm from the skin surface. We have developed the biocompatible Indocyanine Green lotions and the method for in vivo dyeing and dye in depth monitoring. Shift on 16-21 nm of absorption peak of Indocyanine Green to the longer wavelengths due to Indocyanine Green binding with cell proteins in the human skin was found.

Ogiso T., Shiraki T., Okajima K., Tanino T., Iwaki M., Wada T.

Schmook F.P., Meingassner J.G., Billich A.

For the study of in-vitro skin penetration of candidate drugs, excised animal skin is frequently used as a replacement for human skin. Reconstructed human skin or epidermis equivalents have been proposed as alternatives. We compared the penetration properties of human, pig and rat skin with the Graftskin LSE (living skin equivalent) and the Skinethic HRE (human reconstructed epidermis) models using four topical dermatological drugs (salicylic acid, hydrocortisone, clotrimazole and terbinafine) with widely varying polarity. In agreement with published data, pig skin appeared as the most suitable model for human skin: the fluxes through the skin and concentrations in the skin were of the same order of magnitude for both tissues, with differences of at most two- or fourfold, respectively. Graftskin LSE provided an adequate barrier to salicylic acid, but was very permeable for the more hydrophobic compounds (e.g. about 900-fold higher flux and 50-fold higher skin concentrations of clotrimazole as compared to human skin), even more than rat skin. In the case of the Skinethic HRE, we found similar concentrations of salicylic acid as in human skin and an approximately sevenfold higher flux. In contrast, the permeation of hydrophobic compounds through the epidermal layer was vastly higher than through split-thickness human skin (up to a factor of about 800). To conclude, currently available reconstituted skin models cannot be regarded as generally useful for in-vitro penetration studies.

Hadgraft J.

Transport of xenobiotics across the stratum corneum, the rate-controlling membrane of skin, is slow and the mechanism appears complex. However, the basic transfer is controlled by fundamental physicochemical concepts, the predominant of which are partition (K), diffusion (D) and solubility (C_s). In order to change the rate of penetration it is therefore clear that it is these parameters that should be targeted. In most instances enhancement strategies are adopted to improve D, K or C_s, however there are instances in which permeation reduction may be beneficial. Examples include the topical application of sunscreens or insect repellents. This publication demonstrates the way in which modulation effects can be assessed and the difficulties involved in determining which of the physicochemical parameter(s) are being affected. If the formulation influences more than one, synergism can often be seen. Advances in computer modelling have provided an insight into the mechanisms of action of some of the chemical enhancers at a molecular level. Enhanced skin absorption has been reported for the delivery of macromolecules such as insulin (associated with transfersomes) or DNA (as a DOTAP complex). The barrier property of the skin must be modulated for this to be achieved. However the precise mechanisms of action have not been elucidated.

Thepphankulngarm N., Manmuan S., Hirun N., Kraisit P.

Androgenetic alopecia (AGA) is caused by the impact of dihydrotestosterone (DHT) on hair follicles, leading to progressive hair loss in men and women. In this study, we developed caffeine-loaded hollow mesoporous silica nanoparticles coated with ultradeformable liposomes (ULp-Caf@HMSNs) to enhance caffeine delivery to hair follicles. Caffeine, known to inhibit DHT formation, faces challenges in skin penetration due to its hydrophilic nature. We investigated caffeine encapsulated in liposomes, hollow mesoporous silica nanoparticles (HMSNs), and ultradeformable liposome-coated HMSNs to optimize drug delivery and release. For ultradeformable liposomes (ULs), the amount of polysorbate 20 and polysorbate 80 was varied. TEM images confirmed the mesoporous shell and hollow core structure of HMSNs, with a shell thickness of 25–35 nm and a hollow space of 80–100 nm. SEM and TEM analysis showed particle sizes ranging from 140–160 nm. Thermal stability tests showed that HMSNs coated with ULs exhibited a Td10 value of 325 °C and 70% residue ash, indicating good thermal stability. Caffeine release experiments indicated that the highest release occurred in caffeine-loaded HMSNs without a liposome coating. In contrast, systems incorporating ULp-Caf@HMSNs exhibited slower release rates, attributable to the dual encapsulation mechanism. Confocal laser scanning microscopy revealed that ULs-coated particles penetrated deeper into the skin than non-liposome particles. MTT assays confirmed the non-cytotoxicity of all HMSN concentrations to human follicle dermal papilla cells (HFDPCs). ULp-Caf@HMSNs promoted better cell viability than pure caffeine or caffeine-loaded HMSNs, highlighting enhanced biocompatibility without increased toxicity. Additionally, ULp-Caf@HMSNs effectively reduced ROS levels in DHT-damaged HFDPCs, suggesting they are promising alternatives to minoxidil for promoting hair follicle growth and reducing hair loss without increasing oxidative stress. This system shows promise for treating AGA.

Cortesi R., Sguizzato M., Ferrara F.

Ko J., Kim J., Choi S., Kim Y., Park S., Kim J., Kim H., Lee Y., An Y., Hwang N.S.

Protein therapeutics are emerging as essential technologies due to their functional and chemical properties. However, their application is currently limited to delivery by oral and injection methods—the former being inefficient and the latter invasive and potentially tissue damaging. Researchers are, therefore, exploring noninvasive delivery systems for proteins through the skin, including transdermal and topical delivery. The large molecular size of proteins presents a key challenge for skin penetration, hindering their ability to penetrate the dense skin lamellar structure. This review focuses on using nanoparticles as carriers to increase protein stability and enhance skin penetration. The use of noninvasive or minimally invasive enhancers for controlling and improving penetration depth is also examined. Furthermore, the physical properties of nanoparticles that affect delivery are evaluated, aiming to propose ways to advance transdermal and topical delivery methods in the future.

de Mello T., Argenta D.F., Caon T.

Both intrinsic and extrinsic aging lead to a series of morphological changes in the skin including the flattening of the dermal–epidermal junction, increased stratum corneum dryness, reduction in sebaceous gland activity and enzyme activity as well as atrophy of blood vessels. In this study, the impact of these changes on the transport of molecules through the skin was revised. The increase in the number of transdermal formulations on the market in recent decades and life expectancy represent the main reasons for an in-depth discussion of this topic. Furthermore, elderly subjects have often been excluded from clinical trials due to polypharmacy, raising concerns in terms of efficacy and safety. In this way, ex vivo and in vivo studies comparing the transport of molecules through the mature and young skin were analyzed in detail. The reduced water content in mature skin had a significant impact on the transport rate of hydrophilic molecules. The lower enzymatic activity in aged skin, in turn, would explain changes in the activation of prodrugs. Interestingly, greater deposition of nanoparticles was also found in mature skin. In vivo models should be prioritized in future experimental studies as they allow to evaluate both absorption and metabolism simultaneously, providing more realistic information.

Semele R., Grewal S., Jeengar M.K., Singh T.G., Swami R.

Abstract: Psoriasis is an autoimmune systemic chronic inflammatory disease that exhibits characteristic detrimental effects on the skin, often leading to infections or comorbid conditions. The multifaceted nature of psoriasis has made it very challenging to treat, especially with current chemotherapy options. Therefore, it is essential to consider phytoconstituents as novel alternatives. However, despite demonstrating higher anti-inflammatory, anti-psoriasis, and immunomodulatory potential, their clinical usage is hindered due to their poor physicochemical properties. To address these drawbacks, nanoparticulate drug delivery systems have been developed, helping to achieve better permeation of phytoconstituents through topical administration. This has breathed new life into traditional systems of medicine, particularly in the context of treating psoriasis. In this current review, we present a detailed, comprehensive, and up-to-date analysis of the literature, which will contribute to affirming the clinical role of phyto-nano interventions against psoriasis.

Fay E., Jones S., Santos A.F., Flohr C.

There is significant interest in delineating the mechanisms that drive and protect against the development of food allergy (FA) in order to identify ways to intervene. This article will firstly outline the evidence underscoring the skin as a critical site for allergic sensitization, before characterizing how the structure of the human epidermis is specialized to prevent penetration by food antigens and subsequent development of FA. This will be integrated alongside a discussion of the components of the skin barrier that are key to FA prevention. We will then summarize the role of the skin immune system and microbiome in epicutaneous sensitization and FA development. Finally, this article will highlight ways in which the skin barrier might be enhanced to reduce the risk of FA.

Liu Z., He Z., Ai X., Guo T., Feng N.

Androgenic alopecia (AGA) has a considerable impact on the physical and mental health of patients. Nano preparations have apparent advantages and high feasibility in the treatment of AGA. Cardamonin (CAR) has a wide range of pharmacological activities, but it has the problems of poor solubility in water and low bioavailability. There are few, if any, researches on the use of nano-loaded CAR to improve topical skin delivery of AGA. In this study, a CAR-loaded liposomal formulation (CAR@Lip and CAR@Lip Gel) was developed and characterized. The prepared CAR@Lip exhibited a uniform and rounded vesicle in size. CAR@Lip and CAR@Lip Gel can significantly improve the cumulative release of CAR. Additionally, CAR@Lip can obviously promote the proliferation and migration of human dermal papilla cells (hDPCs). Cell uptake revealed that the uptake of CAR@Lip significantly increased compared with the free drug. Furthermore, both CAR@Lip and CAR@Lip Gel groups could markedly improve the transdermal performance of CAR, and increase the topical content of the drug in the hair follicle compared with CAR. The ratchet effect of hair follicles could improve the skin penetration depth of nanoformulations. Notably, Anti-AGA tests in the mice showed that CAR@Lip and CAR@Lip Gel groups could promote hair growth, and accelerate the transition of hair follicles to the growth stage. The anti-androgen effect was revealed by regulating the expression of IGF-1, VEGF, KGF, and TGF-β, participating in SHH/Gli and Wnt/β-catenin pathways. Importantly, the nanoformulations had no obvious skin irritation. Thus, our study showed that CAR-loaded liposomal formulation has potential application in the treatment of AGA.

Yan A., Ruan R., Zhu X., Qiang W., Guan Y., Yu Q., Sun H., Liu M., Zhu H.

The most prevalent kind of hair loss is androgenic alopecia (AGA), which is characterized by hair follicle miniaturization and microenvironment dysfunction. Although topical Minoxidil (MXD) was considered to be a safe and effective treatment for AGA, excess reactive oxygen species (ROS) and lower sulfotransferase activity in the hair follicular microenvironment led to an unsatisfactory treatment of AGA. Here, we developed the ethosome (MTE) load of minoxidil and tocopherol acetate to improve the therapeutic effect of MXD on androgenic alopecia. It could regulate the microenvironment around hair follicles, promote the telogen-to-anagen transition of hair follicles, and boost hair regeneration, thus achieving a synergistic effect of 1+1>2. The results proved that MTE showed excellent stability, biosafety, and good dermal and follicular permeability in vitro. The hair regeneration ability of AGA model mice showed that the co-delivery ethosome might regulate the microenvironment around the hair follicles and improve hair regeneration in comparison to the commercial minoxidil tincture alone. As a result, the strategy provided a promising new strategy for the treatment of AGA.

Dwivedi S., Ahmad I.Z.

Nanotechnology derives from the technology that entailed its designing, production, and application in the nanometer range. Incorporation of nanotechnology in the cosmetic formulation commences the thrust area of research. Nanosized cosmetic formulations offer increased UV protection, penetrate deep into the skin layer, and provide effective release of ingredients, with good solubility and stability. Many of them also exhibit UV protective, antioxidant, and antimicrobial activities. The magnificence of micellar nanoparticles has now become the latest fascinating nanotechnology in the international and local cosmetic market. The micellar nanoparticles effectively enhance the surface area and actively transport the bioactive compounds into the skin. Vesicular nanosystems such as liposome and niosomes are versatile in nature and are able to encapsulate bioactive compounds of different solubilities. Natural compounds with photoprotective activity have created interest in the area of cosmetic formulation since they reduce the oxidative stress, toxicity, and damage caused by radiation. Nanocosmetics can be found in a variety of products ranging from hair care to sunscreen to oral care. The information provided in this chapter about various photoprotection formulations serves as a guide for future research to meet the necessary standards in the cosmeceuticals and cosmetics industries.

Khan N., Jain P., Mohapatra S., Hassan N., Farooq U., Khan R., Talegaonkar S., Mirza M.A., Iqbal Z.

Palakkal S., Cortial A., Frušić-Zlotkin M., Soroka Y., Tzur T., Nassar T., Benita S.

Over the years, extensive research has been carried out to develop new chemical entities for hair loss treatment. Despite these efforts, the newly developed topical and oral treatments have not proven to be curative. Hair loss can result from underlying mechanisms, such as inflammation and apoptosis around hair follicles. We have developed a nanoemulsion based on Pemulen gel for topical application, tentatively addressing both mechanisms. The novel formulation contains two well-known molecules: Cyclosporin A (CsA), an immunosuppressant calcineurin inhibitor, and Tempol, a potent antioxidant. The in vitro permeation study on human skin revealed that the CsA-Tempol gel formulation effectively delivered CsA into the skin's inner target layer, the dermis. The effects of the CsA-Tempol gel on hair regrowth were further demonstrated in the in vivo well-established androgenetic model induced in female C57BL/6 mice. The beneficial outcome was statistically confirmed by quantitative analysis of hair regrowth, measured by color density. The results were further supported by histology analysis. Our findings revealed a topical synergy effect, resulting in lower therapeutic concentrations of both actives unlikely to cause systemic side effects. Overall, our research suggests that the CsA-Tempol gel is a highly promising platform for treating alopecia.

Shaikh Z.S., Patel B.A., Patil S.G., Maniyar A.R.

Anastassakis K.

Anastassakis K.

Leong M.Y., Kong Y.L., Burgess K., Wong W.F., Sethi G., Looi C.Y.

Nano-engineered medical products first appeared in the last decade. The current research in this area focuses on developing safe drugs with minimal adverse effects associated with the pharmacologically active cargo. Transdermal drug delivery, an alternative to oral administration, offers patient convenience, avoids first-pass hepatic metabolism, provides local targeting, and reduces effective drug toxicities. Nanomaterials provide alternatives to conventional transdermal drug delivery including patches, gels, sprays, and lotions, but it is crucial to understand the transport mechanisms involved. This article reviews the recent research trends in transdermal drug delivery and emphasizes the mechanisms and nano-formulations currently in vogue.