Lipid synthesis inhibitors: Effect on epidermal lipid conformational changes and percutaneous permeation of levodopa
AUTOR(ES)
Babita, Kumar
FONTE
Springer-Verlag
RESUMO
A combination of lipid synthesis inhibitors was used to enhance the in vitro and in vivo permeation of levodopa (LD) across rat epidermis, and their influence on epidermal lipids was investigated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Rat epidermis was treated with ethanol and a combination of atorvastatin (750 μg/7 cm2), cerulenin (20 μg/7 cm2), and β-chloroalanine (600 μg/7 cm2) for sustaining the reduced content of epidermal cholesterol, fatty acids (as triglycerides), and ceramide (as sphingosine), respectively, in viable rat skin. This treatment resulted in significant (P<.05) synthesis inhibition of skin lipids up to 48 hours and 6-fold enhancement in the in vitro permeation of LD. The effective plasma concentration of LD was achieved within 1 hour and maintained over 48 hours after topical application to rat epidermis treated with a combination of these lipid synthesis inhibitors. ATR-FTIR studies of inhibitor(s)-treated rat epidermis revealed a significant decrease (P<.05) in peak height and area for both asymmetric and symmetric C−H stretching absorbances, suggesting extraction of lipids. However, an insignificant (P<.05) shift in the frequency of these peaks suggested no fluidization of epidermal lipids by lipid synthesis inhibitors. A direct correlation was observed between epidermal lipid synthesis inhibition, decrease in peak height or area, and percutaneous permeation of LD. Skin lipid synthesis inhibition by a combination of lipid synthesis inhibitors seems to offer a feasible approach for enhancing the transcutaneous delivery of LD.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2750393Documentos Relacionados
- Effect of gramicidin on percutaneous permeation of a model drug
- Dyes as fungal inhibitors: effect on colony diameter.
- EFFECT OF ANTIBIOTICS AND INHIBITORS ON M PROTEIN SYNTHESIS
- Interaction of Chloroplasts with Inhibitors: Location of Carotenoid Synthesis and Inhibition during Chloroplast Development
- Temperature-Induced Protein Conformational Changes in Barley Root Plasma Membrane-Enriched Microsomes: I. Effect of Temperature on Membrane Protein and Lipid Mobility