Optimization of Noscapine-Loaded mPEG-PLGA Nanoparticles and Release Study: a Response Surface Methodology Approach

Abstract

The aim of this study was to incorporate noscapine (Nos) into methoxy poly (ethylene glycol)-poly (lactide-co-glycolide) (mPEG-PLGA) nanoparticles and optimize its size, entrapment efficacy% (EE%), and drug loading% (DL%). Nanoprecipitation was employed for preparation of the nanoparticles. In this respect, the Box–Behnken experimental design was applied to optimize preparation of formulation ingredients and process conditions. Polymer concentration (Polymer Conc.), drug concentration (Drug Conc.), and solvent to antisolvent ratio (S/A) were chosen as independent factors, while size, EE%, and DL% were dependent parameters. Obtained model demonstrated that polymer and drug concentration had direct effects on size while the effect of S/A was non-linear and somehow negligible. Also, to have maximum EE% and DL%, drug Conc. should be at the highest level, while polymer Conc. should be decreased. The optimized sample, with mean ± SD size (nm), EE%, and DL% of 156 ± 17 nm, 98 ± 0.15, and 19.1 ± 0.5, respectively, was achieved experimentally, by utilizing drug Conc. of 0.25% (W/V), polymer Conc. of 0.19% (W/V), and S/A of 0.93. The optimized sample showed spherical shape and monodisperse distribution using scanning electron microscopy. In vitro release profile of the optimized nanoparticles showed a biphasic release pattern for the drug. A 3-month stability study of freeze-dried formulation demonstrated negligible change in size and DL%. The obtained model showed that concentrations of polymer and drug are the dominant factors in determining size, EE%, and DL%.