Permeation kinetics of active drugs through lanolin-based artificial membranes.

Skin-penetration studies play an essential role in the selection of drugs for dermal or transdermal application. In vivo experiments in humans are not always possible for ethical, practical, or economic reasons, especially in the first part of the drug development. It is necessary to develop alternative methods using accessible and reproducible surrogates for in vivo human skin. The in vitro methodologies using biological membranes (human and animal skin) are recognized and well accepted as an alternative but present high inter- and intra-individual variability. Therefore, the formation of synthetic membranes has been studied to obtain skin- mimicking models for permeation studies. The aim of this work is to create lanolin-based artificial membranes that can mimic the absorption through the skin of compounds applied topically. A series of synthetic membranes using two different types of lanolin (water-extracted (WE) and solvent-extracted (SE)) were prepared. Next, the in vitro release test of three drugs (diclofenac sodium, ibuprofen and lidocaine) was performed on artificial membranes and on porcine skin placed on Franz cells. The percentage of release, flux, permeability coefficient, lag time, area under the curve, maximal concentration and time were determined for each compound in the different types of membrane. The results showed that lanolin membranes presented a strong diminution of permeability compared to most artificial membranes, leading to a very similar permeability to that of skin. The SE and WE membranes showed a diminution of transepidermal water loss and permeability of compounds compared with membranes alone. The results from WE membranes were similar to those found for the skin. The lanolin membranes were not capable of perfectly mimicking permeation through the skin, but they did have the same rank order of drug penetration as the skin. It may be deduced from these tests that these systems provide more reliable results for compounds with low to medium lipophilicity. The results demonstrated that new lanolin-based artificial membranes have the potential to be exploited as screening models for determining the permeability of a compound destined to be topically delivered.

[Follicular penetration of nanocarriers is an important penetration pathway for topically applied drugs]. / Bedeutung des follikulären Penetrationswegs für den Wirkstofftransport mittels Nanocarriern.

BACKGROUND: The hair follicle represents a significant penetration route for topically applied substances. ISSUE: The percutaneous absorption of substances can be significantly increased and accelerated by the involvement of hair follicles. In addition, nanoparticles have the characteristic to penetrate deeply and effectively into the hair follicles. MATERIALS AND METHODS: An optimization of drug delivery for topically applied substances is possible if the nanoparticles act solely as a carrier to transport active ingredients into the hair follicle. Once the nanocarrier has penetrated into the hair follicle, the active substance must be released there. This can be triggered by various mechanisms. RESULTS: The released drug can thus pass into the living tissue surrounding the hair follicle independently. With the help of this innovative strategy, the bioavailability of topically applied substances can be significantly improved. CONCLUSION: The transport of active ingredients into the hair follicles with the help of particles and the release of active substances there is a very effective new method for transporting active substances through the skin barrier.

Caffeine delivery in porcine skin: a confocal Raman study.

Confocal Raman microscopy is a novel optical method for studies of pro-drug and drug delivery. This method is a promising technique that enables non-destructive measurement of the permeation profile through skin layers. Peaks of compounds are usually normalised to skin peaks (amino-acid and amide I) for semi-quantitative evaluation. The present study seeks to optimise a methodology for complete quantitative measurement of the amount of an active compound at different depths. Caffeine was used as a tracer to evaluate compound's skin penetration using confocal Raman microscopy. A semi-quantitative depth profile of caffeine was obtained with normalisation of the Raman intensities. These ratios of Raman intensities were correlated with the caffeine concentration using an external calibration curve. The calibration curve was carried out with porcine skin incubated in different concentrations of caffeine; afterwards, each skin sample was analysed by confocal Raman microscopy and HPLC to determine the relation between the Raman signal intensity and the caffeine concentration per skin mass and to create a depth profile. These correlation curves allow the full quantification of the caffeine in skin from Raman intensity ratios at different depths.

Skin permeation and antioxidant efficacy of topically applied resveratrol.

The permeation of resveratrol was assessed by in vitro and in vivo experiments 24 h after topical administration. The in vitro profile of resveratrol was assessed by Raman spectroscopy. Human skin permeation was analysed in vivo by the tape stripping method with the progressive removal of the stratum corneum layers using adhesive tape strips. Moreover, the free radical scavenging activity of resveratrol after its topical application was determined using the DPPH assay. The Raman spectra indicated that the topically applied resveratrol penetrates deep into the skin. The results showed high amounts of resveratrol in the different stratum corneum layers close to the surface and a constant lower amount in the upper layers of the viable epidermis. The concentration of resveratrol present in the outermost stratum corneum layers was obtained by tape stripping after in vivo application. The results demonstrated that resveratrol mainly remained in the human stratum corneum layers. After topical application, resveratrol maintained its antiradical activity. The antioxidant efficacy of the compound was higher in the inner layers of the stratum corneum. As these results have demonstrated, topically applied resveratrol reinforces the antioxidant system of the stratum corneum and provides an efficient means of increasing the tissue levels of antioxidants in the human epidermis.