多西紫杉醇PLGA/nHA复合微球的制备及体外释放研究  

Preparation and in vitro release of Docetaxel loaded PLGA/nHA microspheres

作　　者：李像[1] 魏坤[1] 罗云[2] 高新[2] 赵娜[1] 郭武生[1] 

机构地区：[1]华南理工大学材料科学与工程学院,广东广州510641 [2]中山大学附属第三医院泌尿外科,广东广州510630

出　　处：《中国现代医学杂志》2009年第19期2946-2950,共5页China Journal of Modern Medicine

基　　金：中国高新技术计划(No:2007AA021807);(No:2007AA021908);中国自然科学基金重点项目(No:50732003)

摘　　要：目的制备多西紫杉醇(DTX)聚乳酸羟基乙酸(PLGA)/纳米羟基磷灰石(nHA)复合微球,研究纳米羟基磷灰石对复合微球的载药量,包封率和体外释放等性质的影响,以及抑制前列腺癌细胞的增长效应。方法以疏水性抗癌药物多西紫杉醇作为模型药物,采用单乳化溶剂挥发法(S/O/W)制备PLGA/nHA-DTX复合微球,对载药前后的纳米羟基磷灰石进行透射电子显微镜观察和FTIR分析,并采用扫描电镜、激光粒度仪和高效液相色谱对微球的载药量、包封率、粒径及体外释药性质进行研究。结果FTIR结果表明纳米羟基磷灰石对多西紫杉醇有较强的吸附作用。PLGA/nHA-DTX复合微球的载药量和包封率分别为3.92%和88.7%,较之单纯的PLGA-DTX微球均有很大的提高。经过体外释放药物突释后,复合微球比单纯PLGA微球的药物释放慢。在第30d时,复合微球和单纯的PLGA微球累积药物释率放分别为62.40%和72.70%。MTT实验结果显示PLGA/nHA复合微球对癌细胞增长的抑制效果优于单纯PLGA微球和药物。结论与单纯的PLGA-DTX微球相比,由于纳米羟基磷灰石对多西紫杉醇存在较强的吸附作用,使PLGA/nHA-DTX复合微球的载药量和包封率得到了较大的提高,具有更好的药物缓释效果,抑制癌细胞增长的作用更有效。[ Objectives] To prepare docetaxel （DTX） loaded PLGA/nHA microspheres, research the effect of nHA on drug loading, encapsulation efficiency, in vitro of composite mierospheres and inhibiting the growth of prostate cancers. [ Method ] PLGA/nHA-DTX composite microspheres were prepared by a single-emulsion solvent evaporation method （S/O/W）, with hydrophobie anticaneer doeetaxel as model drug. nHA and drug-loaded nHA were analyzed by TEM and FTIR, and drug loading, encapsulation efficiency, size and in vitro release of mierospheres were studied with SEM, laser particle size analyzer and HPLC, etc. [Results] The results show that nHA have a strong adsorption with DTX. Drug loading and encapsulation efficiency of PLGA/nHA-DTX composite mierospheres were 3.92% and 88.7%, and have greatly improved compared to neat PLGA-DTX microspheres. After initial burst, composite mierospheres released more slowly than neat PLGA mierospheres. At the 30d after in vitro release, the cumulative release rate of composite mierospheres and neat PLGA microspheres were respectively 62.40% and 72.70%. Cytotoxicity test results showed that PLGA/nHA composite microspheres had better effect than PLGA microspheres and DTX to inhibit cancer cell growth. [ Conclusion ] Because nHA has a strong adsorption with DTX, PLGA/nHA-DTX composite microspheres compared to neat PLGA-DTX microspheres enhance drug loading and encapsulation efficiency, and have better drug delivery effect. The effect of inhibiting the growth of cancers of the composite microspheres is also better.

关 键 词：多西紫杉醇 乳酸-羟基乙酸共聚物 羟基磷灰石 复合微球 药物释放 

分 类 号：R943[医药卫生—药剂学]