Preparation and Evaluation of Docetaxel-Loaded Polymeric Nanoparticles for Enhanced Solubility and Bioavailability

Abstract

Docetaxel-loaded PLGA nanoparticles were developed using emulsification solvent evaporation, with the optimized formulation (NP3) showing a drug loading of 3.37 ± 0.19%, loading efficiency of 84.25 ± 4.95%, and process yield of 72.62 ± 9.96%. The nanoparticles had submicron particle sizes ranging from 308.6 to 369.5 nm and moderate zeta potential values between −7.60 and −10.70 mV, indicative of reasonable stability. Microscopic analyses (FESEM and TEM) confirmed spherical morphology and uniform drug distribution. In vitro drug release exhibited an initial burst followed by a sustained release over 30 days, with NP3 releasing the drug slowest (31.22 ± 1.56%). Drug release kinetics suggested diffusion-controlled mechanisms, with NP1 and NP3 fitting Korsmeyer-Peppas models and NP2 aligning with the Higuchi model. FTIR and DSC studies showed no chemical interaction and confirmed the drug’s physical state within nanoparticles. Cytotoxicity assays demonstrated enhanced uptake and greater efficacy of NP3 in liver cancer cell lines while sparing normal cells. Pharmacokinetic evaluation in rats revealed prolonged plasma drug levels, extended mean residence time, increased bioavailability, and higher liver accumulation for NP3 relative to free drug and marketed formulation (Pacliall®). These results highlight the potential of docetaxel-loaded PLGA nanoparticles as effective delivery systems for liver cancer therapy, offering sustained drug release with reduced toxicity.