ASPECTS OF THE TRANSDERMAL DELIVERY OF PROSTAGLANDINS

The skin penetration of prostaglandins E1, E2, F1-alpha and F2-alpha has been studied in vitro in human skin. The absorption rates are influenced by the presence of the enhancers Azone(R) and Transcutol. The results indicated different potential interactions which were structure related. These were further investigated using both bilayers and monolayers of dipalmitoylphosphatidylcholine (DPPC) to mimic stratum corneum lipids. Pretreatment of skin with both Azone and Transcutol was found to facilitate drug fluxes. This was especially the case with the 2-series prostaglandins where, both with, and without enhancer pretreatment, the actual amounts penetrating were greater than for the 1-series. A bilayer model (DPPC multilamellar vesicles) indicated that the 2-series compounds have a greater disruptive effect on structured lipids than their 1-series counterparts. Monolayer experiments demonstrated the mechanism of disruption to be non-penetrative, implying interaction between the 2-series prostaglandins and the DPPC head-group region. The major barrier to prostaglandin penetration appears to reside in the lipid region of the stratum corneum bilayers and the 2-series prostaglandins may interact with polar head-groups in this region in such a way as to ease their passage through them. The reason why the I-series prostaglandins are absorbed comparatively poorly probably lies in their lack of compatibility with the skin membrane constituents and their consequent inability to interact with and destabilize the head-group regions of the stratum corneum lipid bilayers.