Masini V, Bonte F, Meybeck A, Wepierre J
Laboratoire de Pharmacologie, CNRS URA 594, Faculté de Pharmacie, Châtenay Malabry, France.
J Pharm Sci. 1993 Jan;82(1):17-21. doi: 10.1002/jps.2600820104.
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.
脂质体包裹药物的局部生物利用度尚不清楚。我们比较了维甲酸在脂质体和传统酒精凝胶中的皮肤渗透情况。将[3H]二棕榈酰磷脂酰胆碱（DPPC）和[14C]维甲酸（0.14%）包裹于脂质体的磷脂相中，并将[14C]维甲酸加入凝胶中作为对照。采用Franz扩散池进行体外皮肤吸收研究。按照Schaefer法进行皮肤结构的体内分布研究。脂质体可渗透角质层，维甲酸与二棕榈酰磷脂酰胆碱之间存在部分解离。在真皮层，维甲酸单独扩散。维甲酸的释放似乎受到控制，脂质体达到稳态的时间比凝胶更晚。这种现象与吸收显著降低有关（脂质体为1.60%，凝胶为3.09%），且在表皮（主要是角质层）和真皮中的滞留率更高（脂质体形式分别为41%和13%，凝胶形式分别为18%和8%）。这项研究清楚地表明，与凝胶相比，脂质体制剂倾向于改善维甲酸在皮肤中的局部作用并降低全身吸收。
