Long circulating PEGylated poly(d,l-lactide-co-glycolide) nanoparticulate delivery of Docetaxel to solid tumors

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Abstract
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.

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