免疫脂质体包裹的阿霉素对禽成髓细胞瘤病毒感染的药代动力学及化疗效果

Pharmacokinetics and chemotherapeutic efficacy of adriamycin encapsulated in immunoliposomes against avian myeloblastosis virus infection.

作者信息

Dhananjaya K V, Antony A

机构信息

Tumour Biology Laboratory, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.

出版信息

J Virol Methods. 1988 Feb;19(2):121-9. doi: 10.1016/0166-0934(88)90155-3.

DOI:10.1016/0166-0934(88)90155-3

PMID:3366852

Abstract

Immunoliposomes were prepared using rabbit anti-AMV gp80 IgG for the targeted chemotherapy of avian myeloblastosis virus infection. Adriamycin was encapsulated into immunoliposomes and used for in vivo studies. Comparative pharmacokinetics of free drug, drug encapsulated in free liposomes and of drug encapsulated in immunoliposomes in the virus-infected cells revealed that (i) the drug encapsulated in liposomes was cleared from the plasma slowly, and (ii) the drug encapsulated in immunoliposomes accumulated in the target tissue, the bone marrow, 5- and 8.5-fold more than the drug encapsulated in free liposomes and free drug, respectively. The drug encapsulated in immunoliposomes inactivated the virus and exhibited more chemotherapeutic efficacy as compared to controls when injected up to 24 h post-infection. However, when injected 48 h post-infection the drug encapsulated in immunoliposomes did not offer any protection against the virus infection. There is no detectable antibody response against immunoliposomes in the infected animals.

摘要

使用兔抗禽成髓细胞瘤病毒糖蛋白80 IgG制备免疫脂质体，用于禽成髓细胞瘤病毒感染的靶向化疗。将阿霉素包封于免疫脂质体中并用于体内研究。对游离药物、包封于游离脂质体中的药物以及包封于免疫脂质体中的药物在病毒感染细胞中的比较药代动力学研究表明：（i）包封于脂质体中的药物从血浆中清除缓慢；（ii）包封于免疫脂质体中的药物在靶组织骨髓中的蓄积量分别比包封于游离脂质体中的药物和游离药物高5倍和8.5倍。感染后24小时内注射时，包封于免疫脂质体中的药物可使病毒失活，且与对照组相比表现出更高的化疗效果。然而，感染后48小时注射时，包封于免疫脂质体中的药物对病毒感染没有提供任何保护作用。在感染动物中未检测到针对免疫脂质体的抗体反应。