摘要
目的制备奥沙利铂长循环脂质体(long-circulating liposome,LCL),并考察其在体内外的性质。方法利用逆相蒸发法制备奥沙利铂LCL,观察其形态,测定粒径电位、包封率、载药量等理化性质。采用SD大鼠进行药动学研究,考察脂质体在动物体内的药动学参数与生物利用度。结果奥沙利铂LCL的平均粒径为(195.1±1.8)nm,电位为(-29.53±0.57)m V,包封率为18%,载药量为2.4%。药动学研究结果显示,奥沙利铂的血浆清除率是LCL的71倍,LCL能够显著降低奥沙利铂的血浆清除率,延长药物体内滞留时间,LCL的药时曲线下面积(AUC)是奥沙利铂溶液的70倍,显著提高了生物利用度。结论本研究选择逆相蒸发法制备并筛选出具有合适包封率,低毒性和高药效的奥沙利铂LCL。
OBJECTIVE To prepare oxaliplatin long-circulating liposomes（LCL） and perform evaluations in vitro and in vivo. METHODS Oxaliplatin-loaded LCL were prepared by reverse phase evaporation method. Physicochemical properties of LCL were investigated, including particle size and encapsulation efficiency（EE）. Pharmacokinetic study was conducted on rat model. RESULTS The average particle size of oxaliplatin LCL was（195.1±1.8） nm and the potential was（-29.53±0.57） m V. In addition, the encapsulation efficiency was 18% and the drug loading was 2.4%. Pharmacokinetic studies showed that the plasma clearance rate of oxaliplatin is 71-fold LCL, so LCL could significantly reduce the plasma clearance rate of oxaliplatin and prolong drug the residence time in vivo. The AUC of LCL was 70-fold of that for oxaliplatin solution which significantly improved the bioavailability. CONCLUSION This study select reverse phase evaporation method to prepare and obtain the optimal oxaliplatin LCL with suitable entrapment efficiency, low toxicity and high efficacy.
作者
华育晖
汪维佳
王刚
郑小丽
沈雁
HUA Yuhui1, WANG Weijia1, WANG Gang2, ZHENG Xiaoli1, SHEN Yan3(1.Pharmacy Department of Hangzhou Cancer Hospital, Hangzhou First People＇s Hospital Group, Hangzhou 310002, China; 2.Pharmacy Department of Hangzhou First People＇s Hospital, Hangzhou 310006, China; 3.China Pharmaceutical University, Nanjing 211198, Chin)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2018年第3期335-339,共5页
Chinese Journal of Modern Applied Pharmacy
关键词
奥沙利铂
长循环脂质体
理化性质
药动学
oxaliplatin
long-circulating liposome
physicochemical property
pharmacokinetic
作者简介
华育晖，女，副主任药师Tel：15958003407E-mail：hyh87652698@163．com;通信作者：沈雁，女，博士，副教授Tel：13814045497E-mail：shenyan19820801@126．com
