Cutaneous bioavailability in hairless rats of tretinoin in liposomes or gel.

ABSTRACT

Topical bioavailability of drugs incorporated in liposomes is not well known. We compared the skin penetration of tretinoin in liposomes and in a classical alcoholic gel. [3H]Phosphatidylcholine dipalmitoyl (DPPC) and [14C]tretinoin (0.14%) were incorporated in the phospholipidic phase of the liposomes, and [14C]tretinoin was incorporated in a gel for comparison. Skin absorption was studied in vitro with Franz cells. In vivo distribution in cutaneous structures was studied according to Schaefer's method. Liposomes impregnated the stratum corneum, with a partial dissociation between tretinoin and phosphatidyl-choline dipalmitoyl. In dermis, tretinoin diffused alone. Tretinoin release seemed to be controlled, and steady state was reached later with liposomes than with gel. This phenomenon was linked with a significantly reduced absorption (1.60% for liposomes versus 3.09% for the gel) and higher retention in epidermis (mainly stratum corneum) and dermis (41 and 13%, respectively, with liposomal form versus 18 and 8%, respectively, with gel form). This study clearly shows that, compared with the gel, the liposome formulation tends to improve the local effect of tretinoin in the skin and decrease the systemic absorption.