Pharmacokinetics of tazarotene and acitretin in psoriasis.

INTRODUCTION: Psoriasis is a prevalent cutaneous condition with severe physical and psychological manifestations. Since the advent of biologics, clinical outcomes in psoriasis have improved. However, retinoids are useful in the correct clinical context. Tazarotene and acitretin are currently the only US Food and Drug Administration approved retinoids for treatment of psoriasis. Both topical tazarotene and oral acitretin act on retinoic acid receptors and retinoid-X-receptors, resulting in altered gene expression of inflammatory cytokines and inhibition of keratinocyte proliferation. Areas covered: This article provides an in-depth pharmacologic and clinical review on the use of tazarotene and acitretin in psoriasis. The PubMed database was searched using combinations of keywords: acitretin, bioavailability, dosing, efficacy, etretinate, interactions, mechanism, pharmacodynamics, pharmacokinetics, pharmacogenetics, psoriasis, safety, tazarotene, tolerability, and toxicity. Expert opinion: Tazarotene and acitretin are effective treatments for psoriasis. Benefits include lack of immunosuppression and success treating inflammatory psoriasis. When combined with other topical and systemic agents, both retinoids improve clinical efficacy while lowering the treatment threshold. However, topical adherence and bothersome side effects can limit retinoid use. Acitretin and tazarotene both improve outcomes through a unique mechanism that especially benefits subsets of patients, despite side effects and limitations.

Lanolin-based organogel of salicylic acid: evidences of better dermatokinetic profile in imiquimod-induced keratolytic therapy in BALB/c mice model.

The primary aim of the present study was to develop lanolin-based organogel with enhanced delivery potential and reduced skin irritation for the treatment of hyperkeratotic lesions and scaling. The drug was encapsulated in the lipidic bilayers of organogel. The values of particle size, polydispersity index (PDI), and zeta potential of the developed carrier system was found to be 257.5 nm, 0.272, and -24.9 mV, respectively. The system was pseudoplastic in nature with the yield value of 2.3078 Pa. The skin permeation studies exhibited superiority of the prepared lanolin-based organogel formulation over the conventional gel formulation (CGF). Further, the dermatokinetic studies also confirmed better permeation and enhanced skin bioavailability of SA to epidermis as well as dermis vis-à-vis the CGF. In conclusion, the developed organogel system not only improved the delivery profile of SA but also reduced the skin irritant potential. The current findings can provide a suitable alternative for the development of an effective topical formulation of SA for the treatment of hyperkeratotic lesions.

An in vivo confocal Raman spectroscopic investigation of salicylic acid penetration: Variation with formulation parameters.

Salicylic acid (SA) is widely used in leave-on antiacne formulations, typically at a 2% level. As a ß-hydroxy acid, it is a milder active ingredient than either α-hydroxy acids or benzoyl peroxide. SA is a keratolytic agent, a bacteriocide, and a comedolytic agent. For these reasons, improving the efficiency of SA delivery is of interest. The objective of this work is to measure in vivo SA penetration from topically applied 2% SA leave-on products and to understand the penetration in terms of formulation parameters. Penetration of SA was measured in three depth zones-0-3 µm, 3-6 µm, and 6-9 µm below the surface-using in vivo confocal Raman spectroscopy. The delivery of SA from an emulsion, pH 4.0, and a hydrogel, pH 3.75, was compared and contrasted. A comparison of depth profiles reveals, e.g., significant differences in SA distribution between-treatment profiles at various time points after treatment, particularly 3℃6 µm below the surface. The hydrogel exhibited the higher normalized level of SA in the 3-6 µm depth zone. Confocal in vivo Raman spectroscopy is proving to be a valuable tool in determination of details of penetration of products into the skin. The penetration of various 2% SA anti-acne product forms will be compared and contrasted in this presentation. Delivery of SA will be discussed in terms of formulation parameters such as phase, pH, and specific ingredients and molecular-level interactions.

Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy.

Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies.

Acitretin in dermatology.

Acitretin, a synthetic retinoid has gradually replaced etretinate in today's dermatologic practice because of its more favorable pharmacokinetics. Acitretin over the past 20 years has proven useful in a number of difficult-to-treat hyperkeratotic and inflammatory dermatoses and nonmelanoma skin cancers. It is effective both as monotherapy and in combination with other drugs for hyperkeratotic disorders. It is considered to be an established second line treatment for psoriasis and exerts its effect mainly due to its antikeratinizing, antiinflammatory, and antiproliferative effect. Its antineoplastic properties make it a useful agent for cancer prophylaxis. Evidence-based efficacy, side-effect profile, and approach to the use of acitretin would be discussed in this review. In addition to its approved uses, the various off label uses will also be highlighted in this section. Since its use is limited by its teratogenic potential and other adverse effects, including mucocutaneous effects and hepatotoxicity, this review would summarize the contraindications and precautions to be exercised before prescribing acitretin.

Bioequivalence in keratolytic activity of formulations vs its vehicle and comparator formulation: randomized, double-blind clinical trial.

This study assessed the bioequivalence, using keratolytic efficacy, of topical preparations studied in humans using adhesive tape stripping and biophysical methods. Ten healthy patients (3 men and 7 women [7 Caucasians and 3 Asians] mean age, 47 years) completed the study. Each coded product was randomly applied to the back according to the designated time of each sample. In addition, an untreated site (normal skin), and an untreated occluded site (chamber only) served as controls. At the end of the application time, each site was rinsed with tap water and then covered with a plastic chamber for 6 hours. Following removal of the chamber, the site was stripped for protein assay and squamometry analysis. This extends previous observations discerning bioequivalence resulting from different active materials with varying mechanism of action and potency on the skin. Results showed no significant difference between tested products. The novel formulations were of equal keratolytic activity to the "standard" (comparator) and hence bioequivalent in keratolytic activity.

The effects of alcohol on the metabolism and toxicology of anti-psoriasis drugs.

INTRODUCTION: Alcohol has long been suspected to be a triggering and precipitating factor of psoriasis. Alcohol misuse is common in patients with moderate-to-severe psoriasis and appears to impair treatment outcome. AREAS COVERED: In this article, the authors review the available data regarding the metabolic and toxicological interactions between anti-psoriasis systemic drugs and ethanol and/or alcoholic beverages. Special attention is given to the influence of alcohol consumption on the hepatotoxic risk of some anti-psoriasis drugs. The article was prepared using a MEDLINE literature search. EXPERT OPINION: The available knowledge highlights the existence of a few significant pharmacological interactions, such as the reduced exposure to cyclosporine by red wine, the possible increase of cyclosporine levels following a heavy acute alcohol intake, and, especially, the conversion of acitretin to etretinate, in the presence of ethanol, with important implications in females of child-bearing potential. There are limited data on the contributing role of alcohol in the hepatotoxicity induced by some anti-psoriasis drugs and the existing information on this topic is still controversial. However, further investigation is needed to assess the relevance of interactions between alcohol consumption and drug therapy for psoriasis, under both pharmacological and toxicological perspectives. Long-term prospective studies on large cohorts of patients are warranted to disclose the actual significance of such potential interactions in clinical practice.

Acitretin in dermatology: a review.

INTRODUCTION: Acitretin is a systemic retinoid drug used in the treatment of severe psoriasis. It has also been used for a spectrum of other difficult-to-treat dermatoses, including hyperkeratotic and inflammatory dermatoses and non-melanoma skin cancers. Here we review the available data regarding both FDA-approved and off-label uses of acitretin, clinically relevant adverse events, precautions and monitoring. METHODS: A PubMed literature search was conducted utilizing the search term "acitretin," which yielded 714 hits. Results were further limited to English language clinical trials in human subjects. Of 78 articles evaluated for relevance, 60 were included for review. RESULTS: Acitretin is effective as monotherapy and in multidrug therapeutic regimens for the treatment of psoriasis and other hyperkeratotic and inflammatory disorders, as well as for malignancy chemoprevention. Its use is limited by its teratogenic potential and other adverse effects, including mucocutaneous effects and hepatotoxicity. Potential adverse effects may be reduced or avoided by using lower doses of acitretin or in combination with other therapies. LIMITATIONS: The reviewed studies include many small trials and case reports of the use of acitretin for psoriasis. Studies of acitretin therapy for the treatment of other cutaneous disorders are limited. CONCLUSION: Acitretin is a beneficial treatment for psoriasis, and should be considered when not contraindicated. Particularly when used in combination with ultraviolet (UV) phototherapy, is a safe and cost effective therapeutic strategy.

Barrier function of intact and impaired skin: percutaneous penetration of caffeine and salicylic acid.

BACKGROUND: Normally, percutaneous absorption tests are carried out using skin biopsies for an apparent and acceptable physiological condition. However, under different pathological conditions, the stratum corneum (SC) barrier function is impaired. METHODS: The barrier function of the SC was assessed by correlation between the number of repeated applications of tape strips on the skin and its transepidermal water loss (TEWL), as well as by in vitro percutaneous absorption studies of different compounds, using Franz diffusion cells and porcine skin previously stripped. RESULTS: A progressive diminution of the skin barrier function has been detected by TEWL both in vitro and in vivo as the number of skin tape strips increases. On the other hand, the percutaneous absorption of the compounds tested increases in a different way as the number of strips increases. Salicylic acid increases linearly depending on the barrier disturbance. However, percutaneous absorption of caffeine exponentially increased with barrier disturbance. Our results indicate that the barrier impairment of skin always increases the penetration behavior of a given compound; however, the hydrophilic-lipophilic balance of the compounds or formulations used could greatly modify its penetration profile, especially when a modified skin is used. CONCLUSIONS: This in vitro protocol may be useful to simulate the percutaneous absorption profile of some drugs applied onto skin with an impaired SC barrier function and could be used to avoid, to some extent, the use of in vivo experimental animal models in the dermopharmaceutical field.

Two-photon fluorescence excitation microscopy to assess transscleral diffusional pathways in an isolated perfused bovine eye model.

PURPOSE: To assess the feasibility of using two-photon microscopy to study the pattern of diffusion through the sclera of a tracer (tazarotenic acid [TA]). METHODS: Polyvinyl alcohol films containing 1% tazarotenic acid (PVA-TA) were applied to the equatorial sclera of isolated perfused bovine eyes. Two-photon microscopy (TPM) was used to determine the lateral spread and depth of penetration of TA in the sclera over time. Protein and collagen binding were determined, and calibration standards were prepared by TPM imaging at 10 µm depth in scleral samples that had been immersed for 24 hours in solutions of TA of 0.7, 7.0, or 70 µg/mL. RESULTS: TA was weakly bound to collagen and sclera (<55%) but strongly bound to plasma protein (95%). In perfused eyes, 50 minutes after PVA-TA application, peak fluorescence in the sclera was detected at a 210-µm depth. By 85 minutes after application of the PVA-TA film, fluorescence had disappeared from surface layers of the sclera and was at maximum at 250 to 290 µm. Penetration of the tracer followed the track of scleral collagen bundles rather than that of the proteoglycan ground substance between collagen bundles. CONCLUSIONS: TPM can image in real time the progressive diffusion of TA from its source in a PVA-TA film applied to the equatorial sclera of the isolated perfused bovine eye and follow its subsequent penetration deeper into the sclera. The data suggest that lateral spread and deeper penetration of the test compound occurred along the course of scleral collagen bundles. Imaging was possible to a depth of 340 µm, the average thickness of the human equatorial sclera.

A review of acitretin for the treatment of psoriasis.

BACKGROUND: Acitretin is an oral retinoid that is approved for the treatment of psoriasis. It is unique compared to other systemic therapies for psoriasis such as methotrexate and cyclosporine in that it is not immunosuppressive. It is, therefore, safe for use in psoriasis patients with a history of chronic infection such as HIV, hepatitis B, hepatitis C or malignancy who have a contraindication to systemic immunosuppressive therapy and require systemic therapy because topical therapy is inadequate and they are unable to commit to phototherapy. Acitretin is one of the treatments of choice for pustular psoriasis. Even though acitretin is less effective as a monotherapy for chronic plaque psoriasis, combination therapy with other agents, especially UVB or psoralen plus UVA phototherapy, can enhance efficacy. OBJECTIVE: To provide an updated review of the safety and efficacy of acitretin in the treatment for psoriasis. METHODS: Literature review of journal articles from 2008 to 2009 since the last review of acitretin evaluated medical literature from 2005 to 2008. RESULTS/CONCLUSION: Acitretin is an effective systemic therapy for psoriasis and is generally well tolerated at low doses for long-term use. If monotherapy with acitretin is inadequate, it can be used in combination with other treatments, particularly UVB phototherapy, to increase efficacy.

A fully validated HPLC method for the simultaneous determination of acitretin and etretinate in plasma and its application to a pharmacokinetic study in healthy Korean subjects.

OBJECTIVE: Acitretin is used for the treatment of psoriasis. The purpose of this study was to validate an HPLC method for the determination of acitretin and etretinate and to investigate the pharmacokinetic characteristics of acitretin in healthy Korean subjects. MATERIALS AND METHODS: Plasma samples or calibrators were mixed with acetonitrile and retinyl acetate (internal standard). Butanol: acetonitrile (1:1 v/v) and K2HPO4 were added later. After vortexing, 30 microl of the supernatant was injected directly into the analytical column of an HPLC system. The samples were separated by C18 reversed phase HPLC and UV detection was performed at 350 nm. Various assay performances were evaluated. RESULTS: The linearity of acitretin and etretinate was adequate up to 500 ng/ml (R2 = 0.9937 for acitretin and R2 = 0.9923 for etretinate). The accuracy was 89.5 - 113.5% and the precision was satisfactory (within-run CV, 4.4 - 15.8%; between-run CV, 3.3 - 17.4%). The LLOQ was 2 ng/ml and the stability and specificity were satisfactory. However, after storage at room temperature for 24 h under light exposure, the concentrations of acitretin and etretinate decreased by 26.0 - 66.5%. Extraction recovery was 75.1 - 91.5%. Nine healthy Korean subjects were evaluated to study the pharmacokinetics of acitretin. A single oral dose of 30 mg acitretin (Neotigason, Roche Pharmaceuticals) was given to all volunteers. The mean +/- SD pharmacokinetics of acitretin in Koreans were as follows: Cmax 148.7 +/- 93.0 ng/ml, tmax 3.2 +/- 1.3 h, t1/2 81.2 +/- 26.5 h, and AUClast 2641.9 +/- 1274.8 ng h/ml. CONCLUSION: A simple HPLC method for the simultaneous determination of acitretin and etretinate was validated, and the pharmacokinetic characteristics of acitretin in the Korean population were investigated.

Preparation and characterization of chitosan-treated alginate microparticles incorporating all-trans retinoic acid.

Chitosan treated alginate microparticles were prepared with the purpose of incorporating all-trans retinoic acid (ATRA) using an inexpensive, simple and fast method, enhancing dermal localization and sustaining the release of ATRA into the skin. Microparticles characterization, drug-polymer interaction, release profile and in vitro skin retention were investigated. Microparticles presented spherical shape and drug loading capacity of 47%. The drug content of these microparticles was affected by ATRA concentration and by the solvent used and it was more weakly affected by chitosan concentration. The release of ATRA was also affected by chitosan concentration. Microparticles prepared with 0.4% chitosan (w/w) resulted in drug release with a more sustained profile. The results of in vitro retention studies showed that chitosan treated alginate microparticles decreased the drug retention in the stratum corneum (SC), where occur the skin irritation, but maintained the ATRA concentration in the deeper skin layers, where occur the pathologies treated with ATRA. Then, the microparticles developed in this work can be a good candidate to improve the topical therapy with retinoid.

An updated review of acitretin--a systemic retinoid for the treatment of psoriasis.

BACKGROUND: Acitretin is a systemic retinoid used for psoriasis. It normalizes cellular differentiation and maturation and is also used as a chemopreventive agent against cutaneous malignancies. However, it is not used frequently because of its side-effect profile. OBJECTIVE: Safety and efficacy of acitretin was evaluated as monotherapy, as well as in combination with other systemic agents. METHODS: Medical literature from 2005 to 2008 was reviewed. The most scientifically rigorous clinical trials were selected for Psoriasis Area and Severity Index. Articles were limited to case reports or clinical trials, human subjects and English language journals. RESULTS/CONCLUSION: Acitretin is effective as monotherapy for pustular and erythrodermic psoriasis and for plaque psoriasis (with other systemic agents). Side effects of acitretin use occur more commonly with high doses. Hence, acitretin is safe and effective for psoriasis.

Evaluation of skin penetration of topically applied drugs in humans by cutaneous microdialysis: acyclovir vs. salicylic acid.

BACKGROUND AND OBJECTIVE: Cutaneous drug application is used for both local drug therapy and systemic treatment. For both types of treatment, the drug concentration profile in, and transport across, the skin is important. To evaluate skin penetration of topically-applied drugs we recently used cutaneous microdialysis. The aim of this study was the use of this method for studying acyclovir and salicylic acid. METHOD: Five per cent acyclovir cream was applied on intact and tape-stripped skin of healthy volunteers and 5% salicylic acid ointment-onto intact skin of other volunteers. Microdialysis probes with 2 kDa molecular weight cut-off were inserted intradermally and were perfused with Ringer solution. Drug concentrations were measured by high-performance liquid chromatography. RESULTS: Following topical application of 5% acyclovir cream onto intact skin of eight healthy volunteers, no drug was determinable in the skin (cutaneous microdialysate) in any of the subjects studied. After partial removal of the stratum corneum the penetration of this drug into skin increased markedly. The mean maximum skin concentration was about 2 x 5 micromol/L after 2 x 4 +/- 0 x 7 h. Topically applied salicylic acid penetrated intact skin with a maximum concentration in the cutaneous microdialysate of 7 x 57 +/- 3 x 90 micromol/L after 5 x 3 +/- 0 x 4 h. CONCLUSION: Cutaneous microdialysis is a valuable method for estimating skin concentration of topically-applied drug. It allows evaluation after application to a small skin area, of about 2 cm(2), thereby reducing the risk of systemic toxicity. The method may be helpful for evaluating the influence of skin condition on the transport process.

Use of a molecular form technique for the penetration of supersaturated solutions of salicylic acid across silicone membranes and human skin in vitro.

Permeation enhancement of salicylic acid (SA) from supersaturated solutions formed using a 'molecular form' technique was investigated. In a conventional cosolvent technique, two solvents are used, one in which the drug is considerably more soluble than the other. Propylene glycol and water have been predominantly used as cosolvents to create supersaturation in skin permeation enhancement. In this paper, we report the use of buffer solutions with different pHs as media for producing different molecular forms. Supersaturated solutions were prepared using pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model silicone membranes and human skin were used. Hydroxypropyl methyl cellulose (HPMC) was employed to stabilise the supersaturated states. Stability data showed that while the SA supersaturated solutions without HPMC crystallised between 15 min and 46 h depending on the degree of supersaturation, the solutions with HPMC were stable for more than 2 months. The flux of SA increased with the degree of saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture. Although the fluxes of SA with and without HPMC were similar both through silicone membrane and human skin, HPMC was found to be effective in increasing the stability of supersaturated solutions of SA.

Skin penetration of terpenes from essential oils and topical vehicles.

The purpose of this study was to evaluate the in vitro cutaneous penetration of five terpenes--linalool, linalyl acetate, terpinen-4-ol, citronellol and alpha-pinene--applied in pure essential oils or in dermatological formulations (o/w emulsion, oily solution or hydrogel) containing 0.75 % w/w of the essential oils. Different skin absorption was observed depending on the type of the vehicle and terpenes' log P values. Cutaneous accumulation of terpenes is several times higher when they are applied in pure essential oils than in topical vehicles. Penetration of terpinen-4-ol to the skin was better from an oily solution (approximately 90 microg/cm (2)) than from an emulsion (60 microg/cm (2)). No penetration of linalyl acetate from topical vehicles into viable skin was observed, but also for this terpene penetration to the upper layers of the stratum corneum was 2-times higher when an oily solution was used. In contrast, the cutaneous absorption of linalool was the same from both vehicles (50-60 microg/cm (2)). The skin penetration of alpha-pinene was not traceable when it was applied in an oily solution. Only a small amount (approximately 5 microg/cm (2)) of this terpene was determined in viable skin after application as a hydrogel. Citronellol applied in a hydrogel penetrated into all skin layers in a total amount of 25 microg/cm (2), while no penetration into viable skin layers after application of an oily solution was noted. Only citronellol permeated into the acceptor medium.

Melasma: Estudio comparativo de una asociación de ácido glicólico con hidroquinona y peelings de ácido glicólico / Melasma: A comparative study of the combination of glycolic acid and hydroquinone in association with glycolic acid peelings

El melasma es una alteración adquirida de la pigmentación, frecuente, predominante en las mujeres y habitualmente localizado en las áreas de mayor exposición solar de la cara. En el tratamiento de las manchas normalmente se emplean despigmentantes, como la hidroquinona, y fotoprotección. Existen controversias sobre el beneficio de los peelings químicos en el tratamiento del melasma. Comparar la eficacia de una crema despigmentante y un fotoprotector usados aisladamente, así como asociados a peelings de ácido glicólico al 70% en el tratamiento del melasma. Ocho pacientes del sexo femenino participaron en un estudio prospectivo que duró siete meses. Durante el primer mes las pacientes usaron solamente crema con ácido glicólico 10% e hidroquinona 4%, además de fotoprotector, en ambos lados de la cara. Se aplicó, entonces, una secuencia de 4 peelings de ácido glicólico al 70% en un lado de la cara y en el otro lado solamente el vehículo del peeling. Después de 30 días, se realizó una nueva aplicación del peeling y del placebo en lados inversos de la cara. Tres dermatólogos realizaron la evaluación independiente de las fotos clínicas La mayoría de los pacientes tuvo mejora del melasma con el uso de la crema con ácido glicólico al l0% e hidroquinona al4% asociado a la fotoprotección adecuada. La aplicación de los peelings de ácido glicólieo al 70% no produjo aclaramiento del melasma en comparación al placebo y la inversión de los lados de la aplicación confirmó este resultado. El uso de la crema con ácido glicólico al 10% e hidroquinona al 4% asociado a la fotoprotección adecuada es efectivo en el tratamiento inicial del melasma. La aplicación de peelings seria dos de ácido glicólico al 70% no produjo mejora adicional en el aclaramiento de la piel

Melasma is a common acquired pigmentation disturbance, found mainly in women and located generally in those areas of the face most subject to sun exposure. Photoprotection and depigmenting agents, such as hydroquinone, are used in order to lighten the marks. There is, however, some controversy regarding the use of chemical peelings in the treatment of melasma. To compare the efficacy of a depigmenting cream plus sunprotector alone to this same approach in combination with 70% glycolic acid peelings in the treatment of melasma. Eight female patients participated in a split-face prospective study that lasted seven months. During the first month they were oriented to only use a cream containing 10% glycolic acid and 4% hydroquinone as well as sun protector, on both sides of the face. A sequence of 4 peelings using 70% glycolic acid were then applied to one side of the face while only the peeling vehicle was applied to the other side. After 30 days, the application of the peelings and placebo was repeated on inverse sides of the face The treatment was evaluated using clinical pictures assessed by 3 independent dermatologists. Most of the patients showed improvement in their melasma with the use of the 10% glycolic acid and 4% hydroquinone cream together with adequate sun protection. The application of 70% glycolic acid peelings did not result in lightening of the melasma, and the inversion of the sides receiving peelings or placebo confirmed this result. The use of 10% glycolic acid and 4% hydroquinone cream together with adequate sun protection is effective in the treatment of melasma. The application of 70% glycolic acid peelings did not produce additional improvement in the lightening of the affected skin

In vitro percutaneous absorption of all-trans retinoic acid applied in free form or encapsulated in stratum corneum lipid liposomes.

The objective of this study was to design an all-trans retinoic acid (RA) topical release system that modifies drug diffusion parameters in the vehicle and the skin in order to reduce systemic absorption and the side-effects associated with topical application of the drug to skin. Three cases of application of hydrogels containing RA either in free form or encapsulated in stratum corneum lipid liposomes (SCLLs) have been considered. For this purpose, we have evaluated the RA in formulations with combinations of Carbopol Ultrez 10 (U10) and hyaluronic acid (HA) for percutaneous absorption. In vitro permeability experiments with [3H]-t-RA were carried out using a Franz-type diffusion cell in abdominal rat skin samples. Accumulation of the drug in the surface and skin layers was evaluated by both the tape stripping method and a dissection technique, and subsequently, all the radiolabelled samples were analyzed by liquid scintillation counting. The results show that RA encapsulation not only prolongs drug release but also promotes drug retention by the viable skin. At the same time, interaction between RA and HA has an obstructive effect on diffusion, which contributes to the formation of a reservoir of the latter.