Formulation and investigation of 5-FU nanoparticles with factorial design-based studies

This study describes an orthogonal experimental design to optimize the formulation of 5-fluorouracil (5-FU) loaded poly d,l (lactide-co-glycolide) (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement technique. The type of surfactant, amount of acetone and molecular weight of the polymer with three levels of each factor were selected and arranged in an L₁₈(3⁵) orthogonal experimental table. From the statistical analysis of the data polynominal equations were generated. Optimized formulations have the particle size ranging from 160 to 250 nm. Smallest nanoparticles (161 ± 1.22 nm) were obtained using Resomer PLGA 755 and pluronic F-68 with 10 ml acetone amount. Under these conditions the 5-FU entrapment percentage was maximum 78.30%, suggesting 5-FU might be entrapped and adsorbed on the nanoparticle surface. In vitro release of three formulations with maximum drug entrapment efficiency and minimum particle size, were also investigated by release kinetics. According to the determined coefficients, release data fit to Higuchi's diffusion kinetics. The in vitro release of 5FU-NP in phosphate buffered saline (PBS, pH 7.4) is suggested to be controlled by a combination of diffusion with slow and gradual erosion of the particles. Also, the antimicrobial activity was observed even on the end of seventh day with all formulations.