Barrier Properties Of Stratum Corneum Research Articles

Advancements of Polymer-Based Transdermal Drug Delivery Systems in Drug Bioavailability and Patient Compliance in United States

Transdermal drug delivery system (TDDS) helps in overcoming drug molecule barriers such as particle size, lipophilicity, permeability, and transports the medication directly to the blood circulation by employing physical and chemical penetration enhancers using polymers. The use of skin as a drug delivery route is challenging due to the stratum corneum's barrier properties that restrict the therapeutic bioavailability of the medications. Both, natural and synthetic polymers are used in TDDS to transport the medication into circulation via diffusion, and swelling control. TDDS is generally achieved by using transdermal patches containing one or more pharmaceutical active entities that are placed on unbroken skin for delivering active entities directly to the bloodstream by crossing the skin barrier. TDDS is the trendiest -delivery system as it is painless, non-invasive, self-administrative, avoids hepatic first-pass metabolism, and delivers poorly soluble drugs and increases the bioavailability. An overview of TDDS is provided in this review article, including its advantages over traditional dosage forms, limitations, different components of transdermal patches, modern techniques as well as transdermal products available in US market.

Lipo-polymeric nano-complexes for dermal delivery of a model protein.

Delivering macromolecules across the skin poses challenges due to the barrier properties of stratum corneum. Different strategies have been reported to cross this barrier, such as chemical penetration enhancers and physical methods like microneedles, sonophoresis, electroporation, laser ablation, etc. Herein, we explored a cationic lipo-polymeric nanocarrier to deliver a model protein across the skin. A cationic amphiphilic lipo-polymer was used to prepare blank nanoplexes, which were subsequently complexed with anionic fluorescein-tagged bovine serum albumin (FITC-BSA). Blank nanoplexes and FITC-BSA complexed nanoplexes showed sizes of 93.72 ± 5.8 (PDI-0.250) and 145.9 ± 3.2 nm (PDI-0.258), respectively, and zeta potentials of 25.6 ± 7.0 mV and 9.17 ± 1.20 mV. In vitro cell culture, and toxicity studies showed optimal use of these nanocarriers, with hemocompatibility data indicating non-toxicity. Ex vivo skin permeation analysis showed a skin permeation rate of 33% after 24 h. The optimized formulation was loaded in a carbopol-based gel that exhibits non-Newtonian flow characteristics with shear-thinning behavior and variable thixotropy. The nanoplexes delivered via gel demonstrated skin permeation of 57% after 24 h in mice skin ex vivo. In vivo skin toxicity testing confirmed the low toxicity profile of these nanocarriers. These results are promising for the transdermal/dermal delivery of macromolecules, such as protein therapeutics, using nanoplexes.

Dermaplaning for Transdermal Drug Permeation Enhancement: A Qualitative and Quantitative Assessment.

In this study, we sought to investigate the effect of dermaplaning, a popular cosmeceutical skin rejuvenation technique on the permeation of drugs. Baclofen and diclofenac were used as hydrophilic and hydrophobic model drugs, respectively. A specific area of skin was treated with 4 strokes of a dermaplane device. Interindividual variability was assessed by having multiple users operate the device for the study. Dermaplaned skin was histologically evaluated and characterized for resistance drop and the depletion of the stratum corneum (SC). The effect of dermaplaning on drug permeation was investigated via in vitro permeation studies. Histology studies depicted the removal of SC and some parts of viable epidermis by dermaplaning. A significant drop in electrical resistance post skin dermaplaning was observed for all treatment groups, signifying the depletion of barrier properties of SC (p < 0.05). Consequently, significant drug flux and permeation were observed over 24h for the model drugs across dermaplaned skin. However, varied absorption profile was observed in vitro for both drugs across dermaplaned skin. Dermaplaning displayed a better suitability for significantly enhancing the permeation of the hydrophilic drug, baclofen. Evidence of variation in results post dermaplaning was observed amidst multiple users as well (p < 0.05).

Direct assessment of individual skin barrier components by electrical impedance spectroscopy.

Expression of the tight junction proteins Cldn1 and 4 is altered in skin diseases such as atopic dermatitis, and Cldn1 deficiency affects skin barrier formation. Impedance spectroscopy (IS) has been proven to allow detection of alterations in the skin barrier but is currently unable to separate effects on viable epidermis (VE) and stratum corneum (SC). Effects of siRNA-mediated Cldn1 and 4 knockdown in reconstructed human epidermis (RHE) on VE and SC barrier function were investigated with Ussing chamber-based IS. Barrier components were sequentially altered, employing iron oxide nanoparticles and EGTA, to identify their contribution to the impedance spectrum. Resistance changes due to apically applied hyperosmolar electrolyte were used to identify barrier defects non-invasively. IS of RHE yielded two relaxation frequencies, representing the barrier properties of the SC (~1000Hz) and VE (~100Hz). As proof of concept, it was shown that the Cldn1 knockdown-induced resistance drop arises from the impairment of both SC and VE, indicated by a shift of both relaxation frequencies. Hyperosmolar electrolyte penetration allowed non-invasive detection of Cldn1 knockdown via time-dependent frequency shifts. The absence of Cldn4 knockdown-induced changes revealed the weaknesses of transepithelial electrical resistance analysis. In conclusion, the present technique allows to separately measure the barrier properties of SC and VE and further evaluate the Cldn1 and 4 knockdown impact on the skin barrier. As the measurement with agarose-embedded electrolyte allowed non-invasive identification of the Cldn1 knockdown, this opens the way to detailed in vivo skin barrier assessment.

Drug Penetration Enhancement Techniques in Transdermal Drug Delivery System: A Review

Transdermal Drug Delivery System (TDDS) is described as a self-contained or discrete dosage form that is applied to the intact skin. This rout of drug administration of drugs through the skin for therapeutic use is an alternative approach to oral, intravascular, subcutaneous, and transmucosal routes. The delivery of drugs through the skin to the systemic circulation provides a convenient route of administration for a variety of clinical indications. Transdermal Drug Delivery System allows continuous drug administration, use of drugs with short biological half lives, avoids increases hepatic first pass elimination and rapid termination of medication by removing the transdermal drug delivery system from the skin. Various transdermal technologies may be applied for different categories of pharmaceuticals used for the treatment of disorders of the skin or for systemic effects to treat diseases of other organs. Several transdermal products and applications include hormone replacement therapy, contraception, pain management, angina pectoris, smoking cessation, and neurological disorders such as Parkinson's disease. The most commonly used transdermal system is the skin patch using various types of technologies. Stratum corneum is the outermost layer of the skin and it is the main barrier layer for permeation of drug in transdermal delivery of drugs. So, to circumvent the barrier properties of stratum corneum and to increase the flux of drug through skin membrane various penetration enhancement techniques are used in transdermal drug delivery system. The review presents different physical and chemical methods in penetration enhancement approaches and to optimize the transdermal delivery system.

Influencing factors and drug application of iontophoresis in transdermal drug delivery: an overview of recent progress.

Transdermal drug delivery is limited by the stratum corneum of skin, which blocks most molecules, and thus, only few molecules with specific physicochemical properties (molecular weight <500Da, adequate lipophilicity, and low melting point) are able to penetrate the skin. Recently, various technologies have been developed to overcome the strong barrier properties of stratum corneum. Iontophoresis technology, which uses a small current to improve drug permeation through skin, is one of the effective ways to circumvent the stratum corneum. This approach not only provides a more efficient, noninvasive, and patient-friendly method of drug delivery but also widens the scope of drugs for transdermal delivery. In this review, the mechanisms underlying iontophoresis and affecting factors are outlined. The focus will be on the latest advancements in iontophoretic transdermal drug delivery and application of iontophoresis with other enhancing technologies. The challenges of this technology for drug administration have also been highlighted, and some iontophoretic systems approved for clinical use are described.

Simultaneous Measurements of Structure and Water Permeability in an Isolated Human Skin Stratum Corneum Sheet

Stratum corneum (SC), the outermost layer of human skin, acts as an intelligent physicochemical interface between the inside and the outside of our body. To make clear the relationship between structure and physical barrier properties of SC, we developed a method that enables us to simultaneously acquire X-ray diffraction (XD) patterns and transepidermal water loss (TEWL) values using a spread SC sheet isolated from human skin. The synchrotron X-ray was incident on the SC sheet surface at an angle of 45° to avoid interference between the two kinds of measurements. Detailed comparison between XD and TEWL data suggested that the thermal behavior of water permeability is closely related to the thermal expansion of the lattice spacings of the hexagonal phases above 40 °C and to the existence ratio of the orthorhombic phase below 40 °C. Thus, the new method we developed can give useful information on the mechanism of water permeation in SC without ambiguity caused by separate measurements of structure and water permeability with different samples.

Enhanced Transdermal Drug Delivery by Sonophoresis and Simultaneous Application of Sonophoresis and Iontophoresis

Transdermal drug delivery has advantages of topical drug administration compared to the other conventional administration methods. However, the skin penetration of drugs is limited by the barrier properties of stratum corneum. The combinational strategy has been investigated to improve the skin permeability of the drug. For this study, we devised an improved device that can perform not only the single application of sonophoresis or iontophoresis but also the simultaneous application. The enhancement effect of sonophoresis was evaluated for various cosmeceutical drugs using a Franz diffusion cell. The enhancement ratio of niacinamide and retinol with sonophoresis was increased to 402% and 292%, respectively. The relationship was found between the enhancement effect of sonophoresis and the physicochemical properties of drugs. In particular, the simultaneous treatment of sonophoresis and iontophoresis enhanced skin penetration of glutamic acid to 240% using the fabricated device. The simultaneous application showed significantly higher enhancement ratio than application of sonophoresis or iontophoresis alone. Moreover, the improved device achieved skin penetration enhancement of various cosmeceutical drugs with lower intensity and a short application time. This combined strategy of transdermal physical enhancement methods is advantageous in terms of decline in energy density, thereby reducing the skin irritation. The miniaturized device with sonophoresis and iontophoresis is a promising approach due to enhanced transdermal drug delivery and feasibility of self-administration in cosmetic and therapeutic fields.

Dendrimer as a new potential carrier for topical delivery of siRNA: A comparative study of dendriplex vs. lipoplex for delivery of TNF-α siRNA

Topical delivery of siRNA is challenging task due to complex barrier property of stratum corneum and cationic lipid based carriers have been widely explored for this purpose due to improved permeation through skin. For gene delivery application, dendrimers are considered as efficient carrier due to their cationic nature and well-defined surface groups. However, they are not well explored for topical delivery. This work compares the suitability of PAMAM dendrimer with DOTAP liposome for topical delivery of siRNA against TNF-α. The particle size, zeta potential and entrapment efficiency of dendriplex were 99.80 ± 1.80 nm, 13.40 ± 4.84 mV and 98.72 ± 2.02% whereas for lipoplex were 174.80 ± 0.80 nm, 29.96 ± 0.51 mV and 94.99 ± 5.01% respectively. Both the formulations were stable in serum and in the presence of RNAse. TNF-α is inflammatory cytokine, hence the in vivo efficacy of developed formulations was determined using psoriatic plaque model. Results suggested improved phenotypic and histopathological features and reduced levels of IL-6, TNF-α, IL-17 and IL-22 for dendriplex and lipoplex treated groups in comparison to Imiquimod treated group. These findings suggest that dendrimer can be a potential carrier for topical gene delivery.

AN UPDATED REVIEW ON TRANSFERSOMES: A NOVEL VESICULAR SYSTEM FOR TRANSDERMAL DRUG DELIVERY

Transdermal route is an interesting option in this respect because a transdermal route is convenient and safe, avoid first pass metabolism, predictable and extended duration of activity, minimizing undesirable side effects, utility of short half-life drugs, improving physiological and pharmacological responses, avoiding the fluctuation in drug levels and inter and intra-patient variations. However it has got its own limitations its inability to transport large molecules, inability to overcome the barrier properties of stratum corneum and many more. Formulating the drug in a transfersome is one such approach to solve these problems. Transfersome, is an ultradeformable vesicle, elastic in nature which can squeeze itself through a pore which is many times smaller than its size owing to its elasticity. Peer Review History: Received 29 August 2017; Revised 5 September; Accepted 9 September, Available online 15 September 2017 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 4.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Omonkhelin J Owolabi, University of Benin, Nigeria, owolabi@uniben.edu Dr. Taiwo O Elufioye, University of Ibadan, Nigeria, toonitaiwo@yahoo.com Similar Articles: INVESTIGATION OF PRONIOSOMES GEL AS A PROMISING CARRIER FOR TRANSDERMAL DELIVERY OF GLIMEPIRIDE

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different solvents on the outermost layer of skin, the stratum corneum (SC), using polarization transfer solid-state NMR on natural abundance 13C in intact SC. With this approach it is possible to characterize the molecular dynamics of solvent molecules when present inside intact SC and to simultaneously monitor the effects caused by the added solvent on SC lipids and protein components. All solvents investigated cause an increased fluidity of SC lipids, with the most prominent effects shown for the apolar hydrocarbon solvents and 2-propanol. However, no solvent other than water shows the ability to fluidize amino acids in the keratin filaments. The solvent molecules themselves show reduced molecular mobility when incorporated in the SC matrix. Changes in the molecular properties of the SC, and in particular alternation in the balance between solid and fluid SC components, may have significant influences on the macroscopic SC barrier properties as well as mechanical properties of the skin. Deepened understanding of molecular effects of foreign compounds in SC fluidity can therefore have strong impact on the development of skin products in pharmaceutical, cosmetic, and sanitary applications.

Screening sunscreens: protecting the biomechanical barrier function of skin from solar ultraviolet radiation damage.

Solar ultraviolet (UV) radiation is ubiquitous in human life and well known to cause skin damage that can lead to harmful conditions such as erythema. Although sunscreen is a popular form of protection for some of these conditions, it is unclear whether sunscreen can maintain the mechanical barrier properties of skin. The objective of this study was to determine whether in vitro thin-film mechanical analysis techniques adapted for biological tissue are able to characterize the efficacy of commonly used UV inhibitors and commercial sunscreens to protect the biomechanical barrier properties of stratum corneum (SC) from UV exposure. The biomechanical properties of SC samples were assayed through measurements of the SC's drying stress profile and delamination energy. The drying stresses within SC were characterized from the curvature of a borosilicate glass substrate onto which SC had been adhered. Delamination energies were characterized using a double-cantilever beam (DCB) cohesion testing method. Successive DCB specimens were prepared from previously separated specimens by adhering new substrates onto each side of the already tested specimen to probe delamination energies deeper into the SC. These properties of the SC were measured before and after UV exposure, both with and without sunscreens applied, to determine the role of sunscreen in preserving the barrier function of SC. The drying stress in SC starts increasing sooner and rises to a higher plateau stress value after UVA exposure as compared to non-UV-exposed control specimens. For specimens that had sunscreen applied, the UVA-exposed and non-UV-exposed SC had similar drying stress profiles. Additionally, specimens exposed to UVB without protection from sunscreen exhibited significantly lower delamination energies than non-UV-exposed controls. With commercial sunscreen applied, the delamination energy for UV-exposed and non-UV-exposed tissue was consistent, even up to large doses of UVB. In vitro thin-film mechanical analysis techniques can readily characterize the effects of SC's exposure to UV radiation. The methods used in this study demonstrated commercial sunscreens were able to preserve the biomechanical properties of SC during UV exposure, thus indicating the barrier function of SC was also maintained.

Transdermal delivery from liposomal formulations – Evolution of the technology over the last three decades

Strong barrier properties of stratum corneum often limits the efficiency of drug delivery through skin. Several strategies were tried to improve permeation of drug through skin for local as well as systemic drug delivery. Incorporation of the drug within flexible liposomal vesicles has been one of the popular and well-studied approaches for delivering drug to deeper layers of the skin or even systemic circulation. Flexible/deformable/elastic liposomal systems such as invasomes, Transfersomes®, ethosomes, niosomes, etc. have demonstrated encouraging results in delivering small molecules and large proteins to the skin. It is necessary to recognize the promising concepts and analyze their potential, since a clear understanding of the drawbacks and advantages of these approaches will lead towards future development. In the current review we have attempted to give an overview of different liposomal drug carriers for transdermal drug delivery and their efficiency as drug delivery system through different in vivo and in vitro studies. Also, an overview of the studies which investigated the interactions between skin and vesicles, which have lead us to our current understanding of the skin penetration mechanisms of liposomal formulations is presented.

Physical means of stratum corneum barrier manipulation to enhance transdermal drug delivery.

Since the approval of first transdermal patch (Transderm Scop(®)) containing scopolamine in 1979, the improvement in systemic drug delivery through skin remains incremental. The traditional methods based on passive diffusion of drug molecules in to the skin are unable to deliver macromolecules, such as peptides, proteins, DNA and vaccines, due to the barrier properties of stratum corneum (SC). During the course of approximately 35 years, the focuses are not only to overcome the above barrier property of the skin but also the safety, accuracy and patient compliance aspect of the traditional methods. The former limitation can be overcome by altering the SC barrier function by different active methods such electrically assisted methods (sonophoresis, iontophoresis, electroporation, magnetophoresis, pressure waves, electron beam irradiation), SC abruption (microneedles, high-velocity jet) and SC removal (tape-stripping, suction, microdermabrasion, ablation). This review summarizes basic principles, mechanisms, advantages, limitations and recent development of above physical techniques along with skin anatomy and drug transport pathways across skin.

Facial skin pigmentation is not related to stratum corneum cohesion, basal transepidermal water loss, barrier integrity and barrier repair.

Hypotheses have been developed for the evolutionary selection of skin pigmentation one of which relates to improved skin barrier function. The aim of this study was to compare facial skin condition on photoexposed (cheek) and photoprotected (post-auricular) sites of naturally pigmented subjects of different ethnicities (Fitzpatrick skin phototypes II/III and V/VI) and Albino African subjects to understand better the relationship between facial stratum corneum (SC) barrier function, skin surface pH and skin pigmentation. Expert grading of skin conditions, capacitance, skin surface pH and skin barrier function measurements were performed. For the latter, transepidermal water loss (TEWL) measurements before (basal TEWL), after 3, 6 and 9 consecutive tape strippings (SC integrity) and 3.5 and 24 h post tape stripping (barrier recovery) were taken. Amounts of SC protein removed during stripping were estimated using infrared densitometry (SC cohesion). Firstly, correlation analysis of the biometric data of the Black African and Caucasian subjects showed there to be no relationship between skin surface pH and ITA° values nor pH and ITA° with basal TEWL. Neither skin surface pH nor ITA° correlated with SC integrity and barrier recovery measurements, but skin surface pH correlated with SC cohesion. ITA° values were correlated with skin hydration. Secondly, on comparing the three ethnic groups, severe skin photodamage was observed in the Albino African subjects and their SC was thicker. Whereas their basal TEWL was elevated, superior values for SC integrity and barrier recovery were measured. No differences in basal TEWL, SC integrity and barrier recovery were found between the other two subject groups. Equally, SC cohesion and skin surface pH values were similar among the three groups. There was no relationship between ITA° values and basal TEWL, SC integrity, SC cohesion and barrier recovery, but ITA° was correlated with skin hydration. Skin surface pH, irrespective of ITA° values, correlated with SC cohesion, indicating a greater intracorneal cohesion at lower pH values. Thus, pigmentation has no effect on SC barrier properties but was related to skin hydration. On comparing the three ethnic groups, Albino African SC was found to be superior to the Caucasian and Black African subjects in terms of SC integrity and barrier recovery but not basal TEWL. The Albino African subjects also have a thicker SC which contributes to their better SC integrity. No differences in skin barrier functionality or skin surface pH were observed for the other two groups. Skin hydration was, however, greatest in the Black African subjects. Our data support the evolutionary hypothesis that pigmentation protects the skin from UV irradiation and thereby the skin barrier but not the skin pigmentation-/pH-driven adaptive skin barrier hypothesis.

Knock‐down of filaggrin does not affect lipid organization and composition in stratum corneum of reconstructed human skin equivalents

Human skin mainly functions as an effective barrier against unwanted environmental influences. The barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which is composed of corneocytes embedded in an extracellular lipid matrix. The importance of a proper barrier function is shown in various skin disorders such as atopic dermatitis (AD), a complex human skin disorder strongly associated with filaggrin (FLG) null mutations, but their role in barrier function is yet unclear. To study the role of FLG in SC barrier properties in terms of SC lipid organization and lipid composition, we generated an N/TERT-based 3D-skin equivalent (NSE) after knock-down of FLG with shRNA. In these NSEs, we examined epidermal morphogenesis by evaluating the expression of differentiation markers keratin 10, FLG, loricrin and the proliferation marker ki67. Furthermore, the SC was extensively analysed for lipid organization, lipid composition and SC permeability. Our results demonstrate that FLG knock-down (FLG-KD) did not affect epidermal morphogenesis, SC lipid organization, lipid composition and SC permeability for a lipophilic compound in NSEs. Therefore, our findings indicate that FLG-KD alone does not necessarily affect the functionality of a proper barrier function.

Permeability and lipid organization of a novel psoriasis stratum corneum substitute

Lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier properties. The main lipid classes are ceramides, cholesterol and free fatty acids. In previous studies a stratum corneum substitute (SCS) was developed, solely prepared from the SC lipids. The SCS mimics the lipid barrier properties of SC very closely. The present study aimed to design a psoriasis SCS (PS-SCS) mimicking several aspects of the lipid composition in SC from psoriasis patients. This PS-SCS showed a different lipid organization than SCS. The main differences were a reduced presence of an orthorhombic packing and an increased level of crystalline cholesterol. These changes resulted in lower flux of hydrocortisone across PS-SCS than across SCS and SC, which was most likely attributed to the higher level of phase separated crystalline cholesterol in PS-SCS. As propylene glycol (PG) is often used in dermatological formulations, in subsequent studies the interaction of PG with SC and SCS membranes was also investigated. These studies revealed that PG increased the permeability of hydrocortisone, mainly by selectively extracting cholesterol from SCS membranes and SC. This may play an important role in the penetration enhancing effect of PG.

Influence of niacinamide containing formulations on the molecular and biophysical properties of the stratum corneum

Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel methods to probe SC barrier properties in vivo. The aim of the present study was to characterise changes in Trans Epidermal Water Loss (TEWL), corneocyte surface area and maturity, selected protease activities and SC thickness after repeated application of a simple vehicle containing niacinamide. A commercial formulation was also included as a reference. The left and right mid-volar forearms of 20 healthy volunteers were used as study sites, to which topical formulations were applied twice daily for 28 days. After successive tape-stripping, corneocyte maturity and surface area were assessed. In addition, activity of the desquamatory kallikrein (KLK) protease enzymes KLK5 and KLK7, and tryptase and plasmin (implicated in inflammatory process) were measured using a fluorogenic probe assay. The amount of protein removed and TEWL were also recorded. SC thickness before and after treatment was determined using Confocal Raman Spectroscopy (CRS). Overall (i) corneocyte maturity and surface area decreased with increasing number of tape strips, (ii) activity of both the desquamatory and inflammatory enzymes was highest in the outer layers of the SC and decreased with depth (iii) TEWL increased as more SC layers were removed. Furthermore, areas treated with formulations containing niacinamide were significantly different to pre-treatment baseline and untreated/vehicle-control treated sites, with larger and more mature corneocytes, decreased inflammatory activity, decreased TEWL and increased SC thickness. These data (a) confirm the utility of measures and metrics developed previously for the non-invasive assay of SC barrier function, (b) present an holistic picture of a SC compartment managing barrier function through dynamic optimisation of pathlength and quality of building materials used, and (c) shed new light on niacinamide as a topical formulation adjunct with unique SC barrier-augmentation properties.

SC lipid model membranes designed for studying impact of ceramide species on drug diffusion and permeation, Part III: Influence of penetration enhancer on diffusion and permeation of model drugs

The impact of the lipophilic penetration enhancer, oleic acid (OA), on the barrier properties of stratum corneum (SC) lipid model membranes was investigated based on diffusion and permeation studies of model drugs covering a broad range of lipophilicities. Diffusion and permeation experiments of urea, caffeine and diclofenac sodium were conducted using Franz-type diffusion cells. HPLC and capillary electrophoresis techniques were employed to analyze the amount of permeated drug. An incorporation of OA to the SC lipid model membranes did not change the relation between the diffusion and permeation behavior of model drugs presented previously for SC lipid model membranes without OA. The fastest rate of diffusion through SC lipid model membranes occurred in the case of the most hydrophilic drug, urea. In the case of permeation studies of caffeine and diclofenac sodium across SC lipid model systems, the permeability parameters were either equal or slightly larger in favor of the most lipophilic drug, diclofenac sodium. OA had a pronounced impact on the barrier properties of SC lipid model membranes. It caused the impairment of the barrier function of the SC lipid model membrane with Cer [AP] (phytosphingosine-based ceramide), however, surprisingly improved the barrier properties of the SC lipid model system with Cer [EOS] (sphingosine-based acylceramide).

Novel Penetration Enhancers for Skin Applications: A Review

The use of topical formulation is popular over the past decade due to extensive researches made in the field of transdermal drug delivery. As a result, an increasing number of drugs are being added to the list of therapeutic agents that can be delivered to systemic circulation through the skin. Commonly available dosage forms for the topical application are creams, ointments, gels, patches etc. The therapeutic benefits of the above topical formulations are limited due to barrier property of stratum corneum (SC). The use of chemical penetration enhancers (CPEs) is one of the long standing approach to overcome the barrier property of SC. Numerous class of novel compounds have been evaluated for penetration enhancement activity, including soft enhancement for percutaneous absorption (SEPA), for example, 2 N-nonyl-1,3- dioxolanes, N-acetyle prolinate esters (such as pentyl- and octyl-N-acetyle prolinate), alkyldiloxanes (e.g., 1-Alkyl-3-b-D glucopyranosyl-1,1,3,3-tetramethyl disiloxanes), transcarbam (such as 5-(dodecyloxycarbonyl) pentylammonium-5- (dodecyloxycarbonyl) pentylcarbamate), iminosulfurane (like N-hexyl,N-benzoyl-S,S-dimethylimino-sulfuranes), capsaicin derivatives (e.g., Nonivamide), cinnamene compounds (such as cinnamic acid, cinnamaldehyde etc), terpenes (like clove and basil oil) and synergestic combination of penetration enhancers (SCOPE). We briefly describe about the anatomy of skin. Potential mechanisms of action of above novel PEs along with adverse reactions associated with traditional PEs are also considered in this review.