无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。

PREPARTION AND IN VITRO ANTIVIRAL ACTIVITY OF LIPOSOMES OF LIPOPHILIC ESTERS OF ACYCLOVIR

The long chain acyclovir such as the acyclovir laurate and acyclovir palmitate were prepared directly from acyclovir by application of the usual esterification methods with appropriate acyl chlorides. The lipophilic prodrugs were found to be retained easier by liposomes whereas acyclovir escaped readily from liposomes. When assayed in African green monkey cell cultures against herpes simplex virus type I strain, the acyclovir palmitate liposomes proved to be more active compared with the parent drug and its liposome, suggesting an enhanced compatibility between the ester and liposomal lipids and an increased uptake of encapsulated prodrug by infected cells.