Katahira N, Murakami T, Kugai S, Yata N, Takano M
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
J Drug Target. 1999;6(6):405-14. doi: 10.3109/10611869908996847.
To enhance the topical delivery of rhodamine B base (Rho), a model lipophilic compound, the electrostatic interaction between the positive and negative components incorporated in the liposomal bilayer was utilized. The higher in vitro permeability to Rho in rat skin was observed with positive and neutral multilamellar liposomal preparations, the former was prepared with phosphatidylcholine (PC) and stearylamine (SA) and the latter with PC alone, than that given as a solution. Negative liposome composed of PC and dicetyl phosphate (DCP) showed lower skin permeability to Rho. To enhance the Rho retention in the skin, the electrostatic interaction between SA and DCP, which was confirmed by in vitro partition study, was utilized. By pretreating the skin surface with SA solution or empty SA liposome, the skin distribution of Rho given as DCP liposome was substantially enhanced, with increase in the PC distribution into the skin. The pretreatment effect of empty SA liposome was also observed in rats in vivo. In conclusion, it was found that negative DCP liposome provides better drug retention in the skin with lower skin permeability, and the topical drug delivery from DCP liposome was further enhanced by the pretreatment of the skin surface with empty SA liposome.
为提高模型亲脂性化合物罗丹明B碱（Rho）的局部递送效果，利用了脂质体双层中正负组分之间的静电相互作用。与溶液形式给药相比，用磷脂酰胆碱（PC）和硬脂胺（SA）制备的阳性多层脂质体制剂以及单独用PC制备的中性多层脂质体制剂对Rho在大鼠皮肤中的体外渗透性更高。由PC和磷酸二鲸蜡酯（DCP）组成的阴性脂质体对Rho的皮肤渗透性较低。为提高Rho在皮肤中的滞留量，利用了体外分配研究证实的SA和DCP之间的静电相互作用。通过用SA溶液或空白SA脂质体预处理皮肤表面，以DCP脂质体形式给药的Rho在皮肤中的分布显著增强，同时PC在皮肤中的分布增加。在大鼠体内也观察到了空白SA脂质体的预处理效果。总之，发现阴性DCP脂质体在皮肤渗透性较低的情况下能实现更好的药物滞留，并且通过用空白SA脂质体预处理皮肤表面可进一步增强DCP脂质体的局部药物递送。
