IN-VITRO HUMAN SKIN BARRIER MODULATION BY FATTY-ACIDS - SKIN PERMEATION AND THERMAL-ANALYSIS STUDIES

Purpose. This study aims to elucidate the skin permeation enhancement and the skin perturbation effects of a number of fatty acids, i.e. str aight-chain saturated (SFA), monounsaturated (MUFA) and polyunsaturate d acids (PUFA). Methods. The skin permeation enhancement effects were studied using human stratum corneum (SC) and p-aminobenzoic acid (PABA ) as a model permeant. The fatty acids in propylene glycol (FA/PG) wer e applied according to a pre-treatment/co-treatment protocol. The pert urbation effects were studied using differential thermal analysis (DTA ) on SC after pretreatment with FA/PG. Results. SFA with 6 to 12 carbo ns exhibit a parabolic correlation between enhancement effect and chai n-length, with a maximum at nonanoic-decanoic acids (with 9 and 10 car bons). Nonanoic and decanoic acids exert barely noticeable effects on the thermal behaviour of SC, suggesting that they easily mix with the skin lipids. All cis-6-, 9-, 11- or 13-octadecenoic acids (MUFA) enhan ce the permeation of PABA to the same extent. DTA revealed that the ci s-9- and 13-isomers form a separate domain containing mostly the pure fatty acids within the SC lipids and suppress the lipid transitions at 70 degrees 80 degrees C. PUFA-linoleic (LA), or-linolenic (ALA) and a rachidonic acids-enhance PABA permeation stronger than MUFA but additi onal double bonds do not further increase the degree of enhancement. L A and ALA form separate domains but do not completely suppress the SC lipid transitions at 70 degrees/ 80 degrees C. Increase in the enthalp y changes of 70 degrees/80 degrees transitions linearly correlates to the decrease in the permeability coefficients, suggesting that an incr eased perturbation of the skin lipids not necessarily has to yield an increased PABA permeation. Conclusions. The enhancement effects of fat ty acids on the PABA penetration through SC are structure-dependent, a ssociated with the existence of a balance between the permeability of pure fatty acids across SC and the interaction of the acids to skin li pids.