Current Drug Metabolism - Volume 18, Issue 5, 2017

Background: Now-a-days, numerous nanocarrier-based drug products for topical applications are present in the market and number of similar products are being researched. To estimate the amount of drug delivery to skin, the scientists have now established techniques for separation of skin layers for the determination of drug concentrations. This forms the basis of pharmacokinetics of drug(s) in skin, i.e., dermatokinetics. However, dermatokinetic modeling of topical products is still a colossal challenge. Assessment of bioavailability helps in determination of safety and efficacy of topical formulations. Objective: This article is an attempt to explore the usefulness and methodologies of dermatokinetics for nanocarriermediated topical delivery. It also showcases challenges in methodologies used for determination of dermatokinetic parameters along with advantages. Method: All the articles (research and review) used for writing the manuscript were collected from various search engines like Science Direct, Google Scholar, PubMed and Eureka Select using keywords like dermatokinetics, novel drug delivery systems, bioequivalence, bioavailability and topical delivery. Conclusion: As the methods used for determination of pharmacokinetics of oral and intravenous formulations are not useful for dermatokinetic assessment, various methods like tape stripping, microdialysis and vasoconstrictor assays are being used for dermatokinetic assessment. These methods are not only useful to determine the drug concentrations in skin layers, but can also be used to correlate the toxic effects of xenobiotics.

Background: Skin delivery is an exciting and challenging area. There are numerous skin delivery systems available on the market. However, this market still remains limited to a narrow range of substances. Thus, several strategies have been developed to improve the performance of those substances, including the development of nanosystems. Methods: The aim of this review is to elucidate the nanosystems applied to the skin. Thus, we undertook a structured search of bibliographic databases for peer-reviewed research literature. In order to contextualize this subject, anatomy and physiology of the skin will be first briefly described and then general concepts and the various examples of these nanosystems, both cosmetic and pharmaceutical field, will be also accessed. Results: As demonstrated, the use of nanosized carrier systems for drugs or active ingredients has gathered the attention of the most famous cosmetic and pharma industries. In fact, those nanosystems can easily establish a special interaction with skin structures, achieving deeper layers and obtaining a controlled release of the encapsulated substances. Conclusion: The findings of this review confirm the importance of skin delivery and the applications of nanotechnology in this area. Although those nanosystems have a high potential and applicability, there are still some limitations mainly because some of those studies are inconclusive in terms of risk of the nanomaterials and further toxicological investigations could address those issues in order to make these products more functional and attractive to consumers.

Background: Protein and peptides in biological system form an important part of innate immune system and are being explored for potential use in various diseases as therapeutics. Importance of proteins and peptides as a new class of antimicrobial agents has boosted research in the field of biotechnology as potential alternative to antibiotic agents. Objective: Protein and peptides antimicrobial as a therapeutic class are structurally diverse and exhibit potent activity against microbes by various mechanisms. However, they present formidable challenge in formulation due to requirement of specific spatial configuration for their activity and stability. Thus, encapsulation of these therapeutics in various nano-systems may sustain activity along with improvement in stability. Method: The article highlights the need for antimicrobial peptides in dermal infections along with discussion of mechanism of their action. It highlights challenges faced for dermal delivery and research carried out for their successful delivery using nano-systems. Results: It is widely realized that these novel classes of therapeutic agents have tremendous market potential to emerge as an alternative to conventional antibiotic agents for combating issue of multidrug resistant microbial species. Research in their delivery aspects by use of current advances made in delivery systems through use of nanoconstructs offers much needed area for exploration and achieving success. Conclusion: As there is an urgent need for coming up with new therapeutic agents for encompassing the increased burden of microbial diseases in human population as well as their delivery challenges, research in field will give the much-needed strategic advantage against pathogenic organisms.

Background: Melatonin is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective in a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on melatonin for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. Objective: This review focuses on nanocarrier production strategies, dermal melatonin application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted melatonin delivery have also been discussed. Method: In the current review, we have revised relevant articles of the available literature using the major scientific databases. Results: One hundred and thirteen papers were included in the review, the majority of which represent latest researches in nanosized platforms for the dermal delivery of melatonin including liposomes, ethosomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles and cyclodextrins. Furthermore, relevant papers reporting in vitro and in vivo application studies of these nano-based melatonin platforms were also discussed. Conclusion: The use of nanoplatforms for the dermal melatonin delivery as antioxidant agent could improve the efficacy of conventional melatonin administration due to the preservation of the drug from premature oxidation and the enhancement of drug permeation through the skin providing greater exposure times.

Background: Psoriasis is a chronic autoimmune inflammatory skin disease affecting 2 to 3% of people worldwide. Topical therapy as first option in the management of psoriasis is an attractive strategy by delivering drugs efficiently into target sites of disease, minimizing systemic side effects of drugs and ensuring high patient compliance. However, the delivery of antipsoriatic agents via conventional topical formulations is limited due to their poor percutaneous penetration and targeting into deeper layers of the skin. Method: In this review, an overview of skin structure and psoriatic skin as well as different approaches used for the treatment are provided. We discussed the topical nanocarriers including solid lipid nanoparticles, nanostructured lipid carriers, liposomes, niosomes, ethosomes, transfersomes, dendrimers and micelles used to deliver antipsoriatic drugs. We also summarized the 2011 onward research studies dealing with the application of nanocarriers for psoriasis treatment. Result: In the last decades, numerous types of nanocarriers have been widely investigated as a novel delivery approach to reach effective antipsoriatic drug concentrations. These nanocarriers can enhance the therapeutic efficacy and minimize the toxicity of the drugs by lowering the dose. They also improve drug localization in the skin and achieve site-specific drug targeting. But, most of the available studies have lack of clinical outcome in psoriasis and required more focus on the clinical evaluation. Conclusion: Nanocarriers could enhance deposition of antipsoriatic drugs in targeted sites of the skin. Nevertheless, still there is a need to develop more effective simulated models that provide realistic model for psoriasis.

Background: The skin, being the outermost layer of our body, is constantly exposed to oxidative stress induced by UV-radiation, pollutants, smoke and xenobiotics. To counteract the deleterious effects of such exposure, the skin is equipped with a complex anti-oxidation system, involving both exogenous and endogenous antioxidants. As low molecular weight antioxidants undergo depletion in counteracting oxidative stress occurring in the skin, topical supplementation with these agents is regarded as a suitable strategy to restore skin oxidative balance. Unfortunately, most antioxidants show unfavorable physico-chemical properties (e.g. excessive lipophilicity or hydrophilicity, chemical instability) that strongly limit their skin penetration and hence their effectiveness after topical application. To overcome these drawbacks, nanocarriers such as liposomes, niosomes, nanoemulsions and nanoparticles have been widely investigated as dermal delivery systems for antioxidants. Objective: The present paper will review two different types of lipid-based nanocarriers, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which represent the latest innovation in the field of nanoparticles designed as topical drug delivery systems. The effects of loading different topical antioxidants into SLN or NLC will be examined along with the usefulness of these antioxidant delivery systems in improving skin defenses against oxidative stress. Conclusion: In this review, recent studies regarding ability of solid lipid nanoparticles and nanostructured lipid carriers to improve dermal delivery of low molecular weight antioxidants have evidenced that these carriers show technological properties that make them particularly useful for topical delivery of antioxidants, both in pharmaceutical and cosmetic field.

Background: Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. Method: Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. Discussion: In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. Conclusion: The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene.