制备工艺对多柔比星白蛋白纳米粒理化性质、体外释放及药动学的影响  

Effect of Preparation Process of Doxorubicin Albumin Nanoparticles on Physicochemical Properties,in vitro Release and Pharmacokinetics

作　　者：陈祎楠[1] 肖衍宇[1] 苏志桂[1] 平其能[1] 张灿[1] 

机构地区：[1]中国药科大学药学院药剂教研室,江苏南京210009

出　　处：《中国医药工业杂志》2012年第6期432-437,共6页Chinese Journal of Pharmaceuticals

基　　金：国家重大新药创制科技重大专项(2009ZX09310-004);中央高校基本科研业务费专项资金(JKQ2009018;JKP2011005)

摘　　要：分别采用去溶剂化法和乳化交联法制备多柔比星牛血清白蛋白(BSA)纳米粒,以BSA收率、包封率、载药量和粒径等为评价指标,优选处方工艺,并比较两种制备工艺所得制品的差异。结果表明,去溶剂化法和乳化交联法所得纳米粒外观均呈球形,差异不大,BSA收率、包封率、载药量、粒径及电位分别为96.5%、92.9%,98.5%、97.4%,4.3%、3.6%,132.4、172.9 nm,-27.7、-19.9 mV。但制备工艺对体外释放行为和大鼠体内药动学行为影响较大,去溶剂化法和乳化交联法制备的多柔比星BSA纳米粒在生理盐水中48 h累积释放率分别为44.2%、63.8%;大鼠尾静脉给药后,去溶剂化法和乳化交联法所得制品的AUC分别是原药的1.5倍(P<0.05)和1.1倍(P>0.05),前法所得纳米粒在大鼠体内具有一定的缓释效果,而后法所得制品没有。The bovine serum albumin（BSA） nanoparticles loaded with doxorubicin were prepared by desolvation technique and emulsion crosslinking method,respectively.The preparation was optimized with BSA yield,entrapment efficiency,drug loading and particle size as indexes,and the difference of the nanoparticles prepared by two methods were compared.The results showed that there was no significant difference in appearance between two kinds of nanoparticles.The nanoparticles prepared by desolvation technique and emulsion crosslinking method were both spherical with the BSA yield of 96.5% and 92.9%,entrapment efficiency of 98.5% and 97.4%,drug loading of 4.3% and 3.6%, particle size of 132.4 and 172.9 nm,and ζ potential of-27.7 and-19.9 mV,respectively.However,the preparation process had a greater influence on in vitro release and pharmacokinetics in rats.Cumulative release at 48 h of doxorubicin nanoparticles prepared by desolvation technique and emulsion crosslinking method in saline were 44.2% and 63.8%, respecitvely.The AUC in rats after tail vein administration of the products prepared by the above methods were 1.5 times（P0.05） and 1.1 times（P0.05） of bulk drug,respectively.The results showed that the nanoparticles prepared by desolvation technique had a sustained-release profile while the latter products were not.

关 键 词：多柔比星 牛血清白蛋白 纳米粒 去溶剂化法 乳化交联法 理化性质 体外释放 药动学 

分 类 号：R944.9[医药卫生—药剂学]