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)

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

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C_(12)-ACV和C_(16)-ACV),使脂质体包封率从ACV的29.9％提高到C_(12)-ACV的95.6％和C_(16)-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C_(12)-ACV和C_(16)-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C_(16)-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。

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