A series of transdermal permeation enhancers based on dicarboxylic acid esters was studied. Single-chain amphiphiles were markedly more effective than the double-chain ones. Monododecyl maleate, that is a cis derivative, was a more potent enhancer than its trans isomer, while the activity of succinates strongly depended on the donor vehicle. No difference between diastereoisomeric tartaric and meso-tartaric acid derivatives was found.
BACKGROUND: Topical ceramide application is an effective therapeutic approach in skin disorders with disturbed barrier function, including atopic dermatitis and psoriasis. OBJECTIVES: To evaluate ceramide analogue N-tetracosanoyl-(l)-serine tetradecyl ester (14S24) using a novel ex vivo model. METHODS: Freshly excised human skin was disrupted by lipid extraction, tape stripping and sodium lauryl sulphate (SLS) treatment. Barrier perturbation was evaluated by the measurement of transepidermal water loss (TEWL), skin hydration and the penetration of model compound, theophylline (TH), assessed by microdialysis. The effect of topical 5% 14S24 was compared with a commercial formulation containing a skin lipid mixture (LR) and control formulation with no skin lipids (L). RESULTS: Both LR and 14S24 produced significant recovery of TEWL and TH penetration in extracted and tape-stripped skin with 14S24 being significantly more effective. In SLS-treated skin, 14S24 decreased TEWL but not TH penetration; LR was inactive. L improved skin hydration but not barrier characteristics. Weak correlation between TEWL and TH penetration was observed in extracted and tape-stripped skin but not in SLS-treated skin. CONCLUSIONS: Cutaneous microdialysis can serve as a useful tool for the evaluation of skin barrier recovery by topical formulations ex vivo whereas TEWL may not be an appropriate measure of skin barrier function in such studies. The excellent barrier repair activity of 14S24 could be beneficial in skin disorders with ceramide deficiency.
- MeSH
- ceramidy farmakologie MeSH
- detergenty MeSH
- dodecylsíran sodný MeSH
- dospělí MeSH
- financování organizované MeSH
- kožní absorpce účinky léků MeSH
- kůže metabolismus účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrodialýza metody MeSH
- perspiratio insensibilis účinky léků MeSH
- preklinické hodnocení léčiv metody MeSH
- rozpouštědla MeSH
- serin analogy a deriváty farmakologie MeSH
- techniky tkáňových kultur MeSH
- tělesná voda metabolismus MeSH
- theofylin farmakokinetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
A simple HPLC/UV method for the determination of the transdermal permeation and dermal penetration of a broad-spectrum antiviral drug adefovir (PMEA) was developed. The separation was achieved on a C18 column with the mobile phase composed of 10 mM KH2PO4 and 2 mM Bu4NHSO4 at pH 6.0 and 7% acetonitrile. The method was validated with respect to selectivity, linearity (0.1-50 microg/ml), precision, accuracy, and stability. Transdermal permeation of 2% PMEA was studied in vitro using the Franz diffusion cell and porcine skin. The flux values were 1.8, 3.0, and 0.6 microg/cm2/h from aqueous donor samples at pH 3.4 and 7.4, and isopropyl myristate, respectively. The respective skin concentrations at 48 h were 294, 263, and 971 microg/g from these vehicles. These results will serve as a lead for further studies on transdermal and topical delivery of antivirals from the group of acyclic nucleoside phosphonates.
- MeSH
- adenin analogy a deriváty analýza aplikace a dávkování MeSH
- antivirové látky analýza aplikace a dávkování farmakokinetika MeSH
- aplikace kožní MeSH
- financování organizované MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- organofosfonáty analýza aplikace a dávkování farmakokinetika MeSH
- prasata MeSH
- reprodukovatelnost výsledků MeSH
- spektrofotometrie ultrafialová metody MeSH
- techniky in vitro MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
