Senthilkumar Murugesan, Mishra Pradeep, Jain Narendra Kumar
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr HS Gour University, Sagar, MP, India.
J Drug Target. 2008 Jun;16(5):424-35. doi: 10.1080/10611860802088598.
The aim of this study was to investigate the ability of PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (NPs) to deliver Docetaxel (DTX) (an anticancer agent) to solid tumors.
PLGA-mPEG diblock copolymers were synthesized by ring opening polymerization reaction and characterized by (1)H NMR, FT-IR and gel permeation chromatography. NPs, with a smooth spherical shape and near 100 nm size were prepared using the emulsion solvent evaporation technique and characterized. The drug release rate was investigated in acidic and physiological media (phosphate buffer saline, pH 5.0 and 7.4). The therapeutic efficacy and biocompatibility of NP formulations were evaluated for in vitro cytotoxicity by MTT assay using MCF-7 and C26 cell lines. The pharmacokinetic and biodistribution studies were performed on C26 tumor bearing mice. The antitumor efficacy of DTX NP formulations on C26 tumor bearing mice was investigated.
DTX-loaded PEGylated NPs increased the drug's biological half-life while providing substantial accumulation at the solid tumors. PEGylated NPs appear to be a promising alternate carrier for DTX having greater efficacy in inhibiting tumor growth.
本研究旨在探究聚乙二醇化聚（D，L-丙交酯-共-乙交酯）纳米粒（NPs）将多西他赛（DTX，一种抗癌药物）递送至实体瘤的能力。
通过开环聚合反应合成聚乳酸-羟基乙酸共聚物-聚乙二醇二嵌段共聚物，并采用核磁共振氢谱（¹H NMR）、傅里叶变换红外光谱（FT-IR）和凝胶渗透色谱法对其进行表征。使用乳液溶剂蒸发技术制备出形状光滑呈球形且尺寸接近100 nm的纳米粒，并对其进行表征。在酸性和生理介质（磷酸盐缓冲盐水，pH 5.0和7.4）中研究药物释放速率。采用MTT法，使用MCF-7和C26细胞系对纳米粒制剂的治疗效果和生物相容性进行体外细胞毒性评估。对荷C26肿瘤小鼠进行药代动力学和生物分布研究。研究DTX纳米粒制剂对荷C26肿瘤小鼠的抗肿瘤疗效。
负载DTX的聚乙二醇化纳米粒延长了药物的生物半衰期，同时在实体瘤中实现了大量蓄积。聚乙二醇化纳米粒似乎是一种有前景的DTX替代载体，在抑制肿瘤生长方面具有更高的疗效。
