紫杉醇热敏脂质体制备及抗肿瘤作用评价  

Preparation of thermosensitive liposomes containing paclitaxel and their anticancer effect

作　　者：尤晓惠[1,2] 张慧[2] 潘见[1] 付盟[2] 梅兴国[2] 胡富强[3] 

机构地区：[1]合肥工业大学农产品生物化工教育部工程研究中心,合肥230009 [2]军事医学科学院毒物药物研究所,北京100850 [3]浙江大学药学院,杭州310058

出　　处：《军事医学》2011年第3期219-222,共4页Military Medical Sciences

基　　金：国家"973"计划资助项目(2009CB30305);国家重大新药创制科技重大专项资助项目(2009ZX09301-002)

摘　　要：目的制备紫杉醇热敏脂质体（PTL）并考察其抗肿瘤作用。方法采用薄膜分散法制备PTL及紫杉醇普通脂质体（PL）;高效液相色谱（HPLC）法测定体内外紫杉醇的含量。建立小鼠Lewis肿瘤模型,随机分为4组,即对照组、紫杉醇注射液（PTX）组、PL组和PTL组,每组给药后均对肿瘤部位加热30 min,监测肿瘤的体积及小鼠生活状态,考察抑瘤效果。结果制备的PTL粒径分布在70~140 nm,包封率约为99%,相变温度约为42℃;体内热敏实验中,PTL组加热部位药物浓度明显高于PTX组和PL组加热部位;PTX组、PL组和PTL组的抑廇率分别为49.79%、57.40%和75.66%。结论与PTX和PL相比,PTL具有明显的热敏靶向性,与热疗相结合显著提高了紫杉醇的治疗效果。Objective To prepare the thermosensitive liposomes containing paclitaxel（PTL）and study their anticancer effect.Methods Both PTL and paclitaxel liposomes（PL） were prepared by the thin-film method.The HPLC method was established to determine paclitaxel concentration in vivo and in vitro.The model of mice Lewis sarcoma was established and divided into four groups randomly：control,PTX,PL and PTL groups.Each group was administrated with drug and local hyperthermia for 30 min.The volume and weight of tumor were detected.Results The mean particle size of the liposomes ranged 70-140 nm and the drug entrapment efficiency was about 99%.The phase transition temperature of PTL was about 42℃.In vivo,the study of thermosensitive characteristics of PTL indicated that drug content in heated location was significantly higher than that of the unheated.The inhibition ratio of tumor in PTX,PL and PTL groups was 49.79%,57.40% and 75.66%,respectively.Conclusion Compared with PTX and PTL,PTL has an evident thermosensitive characteristic and increases the anticancer effect of paclitaxel remarkably when combined with hyperthermia.

关 键 词：紫杉醇 脂质体 热敏 抗肿瘤作用 

分 类 号：R944.9[医药卫生—药剂学] R979.1[医药卫生—药学]