Biocompatibility, Efficacy and Biodistribution of Gelucire-Stabilized Nanoparticles Engineered for Docetaxel Delivery
Docetaxel is a potent anticancer agent that will benefit greatly from alternative delivery systems that can overcome several reported adverse effects due to the drug itself and/or the solvent system in the current clinical formulation. In this regard, a new nanoparticle delivery system for docetaxel was prepared from Gelucire-based nanoemulsions by using binary mixtures of Gelucire 44/14 and cetyl alcohol as NP matrix materials. Various amounts of docetaxel (50–1000 μg/ml) were added to the oil phase of the nanoemulsions prior to obtaining solid nanoparticles. The nanoparticles (100–140 nm) achieved high entrapment efficiency (≥89%) of docetaxel which was maintained upon storage at 4 °C and 25 °C. Additional data indicated the Gelucire component in NP played influential roles in drug release possibly by facilitating diffusion from NPs and/or accelerating erosion of NP matrix. Docetaxel-loaded nanoparticles did not cause any significant red blood cell lysis or platelet aggregation nor activate macrophages. Also in-vitro antitumor efficacy in human lung adenocarcinoma cells was demonstrated based on cell cytotoxicity, production of reactive oxygen species and reduction of mitochondrial potential. Enhancement of in-vitro antitumor effects of docetaxel with Gelucire-based NPs could be ascribed to improved particle dispersion and efficient cell permeability. Studies in BALB/c mice demonstrated the stability/retention of NPs in blood circulation and the potential in facilitating docetaxel absorption across the peritoneal cavity. The nanoparticles reported herein may be effective as novel biocompatible and effective delivery systems for docetaxel.
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Document Type: Research Article
Publication date: 2012-03-01
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