PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti-tumor activity in BT-549 cells and in vivo evaluation
PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti-tumor activity in BT-549 cells and in vivo evaluation
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DOI：
10.1007/s12034-012-0313-7
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发表时间：
2012-06-01
影响因子：
1.8
通讯作者：
Nayanabhirama, Udupa
中科院分区：
文献类型：
--
作者：
Averineni, Ranjith K.;Shavi, Gopal V.;Nayanabhirama, Udupa
由于紫杉醇的溶解性差，阻碍了其临床应用，这就需要开发新的药物释放系统来传递这种极端疏水的药物。制备适合于有效地(静脉)输送疏水性药物的纳米粒，以用于乳腺癌的治疗；在此背景下，使用BT-549细胞株进行体外细胞毒活性的评估。采用乳化溶剂挥发法制备了PLGA纳米粒，并对其理化参数、体外抗肿瘤活性和体内药代动力学进行了评价。在优化处方中得到的微球粒径为200 nm。包封率在20：1时较高。体外释药呈现先爆发释放后缓慢持续释放(15d)的两相模式。优化处方的体外抗肿瘤活性对BT-549细胞的生长抑制时间为168h。纳米粒的AUC((0-a))和t(1/2)较高，清除率较低。
Clinical administration of paclitaxel is hindered due to its poor solubility, which necessitates the formulation of novel drug delivery systems to deliver such extreme hydrophobic drug. To formulate nanoparticles which makes suitable to deliver hydrophobic drugs effectively (intravenous) with desired pharmacokinetic profile for breast cancer treatment; in this context in vitro cytotoxic activity was evaluated using BT-549 cell line. PLGA nanoparticles were prepared by emulsion solvent evaporation technique and evaluated for physicochemical parameters, in vitro anti-tumor activity and in vivo pharmacokinetic studies in rats. Particle size obtained in optimized formulation was < 200 nm. Encapsulation efficiency was higher at polymer-to-drug ratio of 20:1. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release (15 days). In vitro anti-tumor activity of optimized formulation inhibited cell growth for a period of 168 h against BT-549 cells. AUC((0-a)) and t (1/2) were found to be higher for nanoparticles with low clearance rate.