INFLUENCE OF LIPOSOMAL ENCAPSULATION ON THE PENETRATION OF RETINOIC ACID THROUGH HUMAN SKIN IN-VITRO

The penetration of liposome-encapsulated trans-retinoic acid (t-RA) th rough the different strata of the skin was investigated using in vitro diffusion experiments on human cadaver skin. Simple phospholipid lipo somes and a more complex pH-sensitive preparation containing 0.05% t-R A were applied to isolated human stratum corneum, isolated human epide rmis, and dermatomed human skin, along with one of two nonliposomal co ntrols. The control solutions were either 0.05% t-RA in ethanol (for s mall-dose experiments) or saturated solutions of t-RA in Transcutol(R) /water mixtures (for large-dose experiments and some small-dose experi ments). Skin-specific interactions were differentiated from solution t hermodynamic effects by repeating some experiments using a silicone ru bber membrane. The influence of dose volume and occlusion was investig ated. The results showed no evidence of enhanced epidermal penetration , nor of decreased percutaneous absorption from liposomal t-RA vs unen capsulated controls under realistic dose conditions. However, under on e see of exaggerated dose conditions (consisting of a large, non-occlu ded dose of t-RA in PC liposomes), there was a suggestion that diffusi on of t-RA across the lower skin layers may have been retarded by the liposomal components.