Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation
Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation
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DOI：
10.1016/j.jconrel.2008.09.086
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发表时间：
2009-01-05
影响因子：
10.8
通讯作者：
Preat, Veronique
中科院分区：
文献类型：
--
作者：
Danhier, Fabienne;Lecouturier, Nathalie;Preat, Veronique
本研究的目的是开发不含Cremophor（R）EL的纳米颗粒，该纳米颗粒装载有Paclitaxel（M），旨在静脉内给药，能够提高药物的治疗指数，并且没有Cremophor（R）EL的副作用。采用简单乳液法和纳米沉淀法制备了载紫杉醇的聚乙二醇化聚乳酸-羟基乙酸共聚物复合物，纳米沉淀法具有较高的载紫杉醇效率。PTX的释放行为表现出双相模式，其特征在于初始突释，随后缓慢且连续的释放。使用人宫颈癌细胞（HeLa）通过MTT试验评估体外抗肿瘤活性，并与商业制剂Taxol和Cremophor EL进行比较。当暴露于25 μ g/ml的M时，负载M的纳米颗粒的细胞活力低于Taxol（IC 50 5.5 vs 15.5 μ g/ml）。流式细胞术研究表明，紫杉醇负载的纳米粒子的细胞摄取是浓度和时间依赖性的。HeLa细胞暴露于紫杉醇（R）和M-负载的纳米颗粒诱导相同百分比的凋亡细胞。与Taxol（R）相比，负载M的纳米颗粒在体内对TLT肿瘤显示出更大的肿瘤生长抑制作用。因此，负载M的纳米颗粒可以被认为是用于癌症化疗的有效抗癌药物递送系统。(C)2008年由Elsevier B. V.出版。
The purpose of this study was to develop Cremophor (R) EL-free nanoparticles loaded with Paclitaxel (M), intended to be intravenously administered, able to improve the therapeutic index of the drug and devoid of the adverse effects of Cremophor (R) EL. PTX-loaded PEGylated PLGA-based were prepared by simple emulsion and nanoprecipitation.The incorporation efficiency of PTX was higher with the nano precipitation technique. The release behavior of PTX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The in vitro anti-tumoral activity was assessed using the Human Cervix Carcinoma cells (HeLa) by the MTT test and was compared to the commercial formulation Taxol (R) and to Cremophor (R) EL When exposed to 25 mu g/ml of M, the cell viability was lower for M-loaded nanoparticles than for Taxol (R) (IC50 5.5 vs 15.5 mu g/ml). Flow cytometry studies showed that the cellular uptake of PTX-loaded nanoparticles was concentration and time dependent. Exposure of HeLa cells to Taxol (R) and M-loaded nanoparticles induced the same percentage of apoptotic cells. M-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol (R) Therefore, M-loaded nanoparticles may be considered as an effective anticancer drug delivery system for cancer chemotherapy. (C) 2008 Published by Elsevier B.V.