壳聚糖包覆米托蒽醌脂质体在荷瘤小鼠体内的组织分布及药效学  

Tissue distribution and pharmacodynamics of chitosan-coated mitoxantrone liposomes in the tumor-bearing mice

作　　者：庄婕[1] 石勇平[1] 平其能[1] 苏志桂[1] 崔征[1] 宋赟梅[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009

出　　处：《中国药科大学学报》2010年第4期353-359,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30873183)~~

摘　　要：考察了壳聚糖包覆米托蒽醌脂质体(CL-MTO)的体外释放以及在荷黑色素瘤小鼠体内的组织分布及药效。采用透析法测定CL-MTO的体外释放度,通过荷瘤小鼠尾静脉注射米托蒽醌溶液剂(I-MTO)、米托蒽醌脂质体(L-MTO)和CL-MTO,考察3种制剂的体内分布特征和靶向性,通过抑瘤率评价药效。结果表明,CL-MTO和L-MTO在pH6.0～7.4的释放介质中24h累积释放百分率分别为30.81%～16.15%和41.84%～32.51%。壳聚糖包覆延缓了脂质体的体外释放。与I-MTO相比,两种脂质体的血浆AUC显著增加,心、肾分布减少;CL-MTO的血液AUC与网状内皮系统AUC之比是L-MTO的1.70倍,肿瘤相对摄取率为L-MTO的1.74倍,且药效增强。壳聚糖包覆增加了脂质体的体内外稳定性以及肿瘤靶向性,提高了疗效。In vitro release,tissue distribution and pharmacodynamics of chitosan-coated mitoxantrone （ MTO） liposomes （ CL-MTO） in tumor-bearing mice were investigated. In vitro releases of CL-MTO and mitoxantrone liposomes （ L-MTO） were determined by dialysis. After intravenous injection of I-MTO （ mitoxantrone saline solution） ,L-MTO and CL-MTO to tumor-bearing mice, levels of MTO in the biological samples were assayed by HPLC,and the tissue distribution and targeting performance of the three different formulations were evaluated, and their pharmacodynamics were determined by their antitumor efficacy. It was found that the cumulative release of CL-MTO and L-MTO in various dissolution media （ pH 6. 0-7. 4 ） were around 30. 81%-16. 15% and 41. 84%-32. 51% ,respectively. Chitosan-coating retarded in vitro release of MTO from the liposomes. If compared to I-MTO,the study of tissue distribution of CL-MTO and L-MTO proved that the area under the plasma concentration-time curve （ AUCplasma） increased significantly,while the area under the heart and kidney tissue level-time curve （ AUCheart and AUCkidney） decreased. The ratio of the AUC of plasma to that AUC of reticulo-endothelial system （ Blood /RES） of CL-MTO was 1. 70-fold higher than that of L-MTO. Moreover,there existed higher relative tumor exposure （ 1. 74-fold） and higher therapeutic efficacy of CL-MTO than L-MTO. This study indicated that chitosan-coating increased in vitro /in vivo stability of liposomes and their tumor-targeting potentials,as well as improved the therapeutic efficacy of liposomes.

关 键 词：壳聚糖 米托蒽醌脂质体 释放度 组织分布 药效学 

分 类 号：R96[医药卫生—药理学]