du Plessis J, Egbaria K, Ramachandran C, Weiner N
College of Pharmacy, University of Michigan, Ann Arbor 48109.
Antiviral Res. 1992 Jun;18(3-4):259-65. doi: 10.1016/0166-3542(92)90059-e.
The extent of uptake of gamma interferon (gamma-IFN) in various strata of hairless mouse, human and hamster skin upon application of a liposomal formulation and an aqueous solution were determined by in vitro diffusion cell experiments. For each of the animal species studied, 70-80% of the liposomally entrapped IFN was deposited onto or penetrated into the skin as determined 24 h after in vitro application. However, a significant fraction of this total amount (approximately 0.25-0.30) is either adsorbed to or associated with the stratum corneum. The drug content found in the deeper skin strata, where the receptor sites reside, suggests that drug deposition is strongly influenced by the skin species tested. The percent of applied drug found in this strata 24 h after application followed the order: hamster (6.1) much greater than human (0.9) greater than hairless mouse (0.3), although the amounts of drug in the total skin of each species tested were approximately the same. This indicates that the deposition of drug into the living epidermis and/or dermis cannot be predicted by determination of the amount of drug in the total skin. The amounts in the deeper skin strata were also in the order of increasing number of follicles/hair in the skin species, suggesting that the transfollicular route is an important pathway for liposomal topical therapeutics.
通过体外扩散池实验,测定了脂质体制剂和水溶液在无毛小鼠、人类和仓鼠皮肤各层中γ干扰素(γ-IFN)的摄取程度。对于所研究的每种动物物种,体外给药24小时后测定发现,脂质体包裹的IFN中有70%-80%沉积在皮肤表面或渗透进入皮肤。然而,这一总量的很大一部分(约0.25-0.30)被角质层吸附或与之结合。在受体所在的更深层皮肤中发现的药物含量表明,药物沉积受到所测试皮肤物种的强烈影响。给药24小时后在该层中发现的给药量百分比顺序为:仓鼠(6.1)远大于人类(0.9)大于无毛小鼠(0.3),尽管所测试的每个物种的全皮药物量大致相同。这表明,不能通过测定全皮药物量来预测药物向活表皮和/或真皮中的沉积。更深层皮肤中的药物量也按照皮肤物种中毛囊/毛发数量增加的顺序排列,这表明经毛囊途径是脂质体局部治疗的重要途径。