Optimization of paeonol-loaded poly(butyl-2-cyanoacrylate) nanocapsules by central composite design with response surface methodology together with the antibacterial properties

Abstract

With the aim to enhance dissolution rate and bioavailability of paeonol, paeonol-loaded poly(butyl-2-cyanoacrylate) nanocapsules (Pae@PNCs) were prepared by interfacial spontaneous polymerization for the first time. Herein, a rotatable central composite design (RCCD) with three-factor five-level was applied to evaluate the optimization experiments. To the maximum percentage encapsulation efficiency (EE%) and minimum particle size (nm) of the Pae@PNCs, a quadratic polynomial model was generated to predict and evaluate the independent variables with respect to the dependent variables. RSM model goodness fitting were confirmed by the ANOVA Table (P<0.05) through variance analysis, which predicted values of EE (%) and particle size (R2 and adjusted R2 were close to 1, respectively) in good agreement with experimental values. By solving the regression equation and analyzing the response surface, three-dimensional model graphs and plots, the optimal result for the preparation of Pae@PNCs were found to be: pH (2.34), Poloxamer F-68 (0.80% m/v) and ethyl acetate/α-BCA ratio (16.67 v/v) for the highest EE% (73.58±2.76%) and the smallest particle size (42.06±1.20nm). The release profiles and antibacterial activity in vitro from the optimal Pae@PNCs were performed. The results indicated that it has slow and well-controlled release, and has strong antibacterial activity in vitro than paeonol. This understanding can help to predict the conditions of optimization of poly(butyl-2-cyanoacrylate) nanoparticles formation and to improve paeonol bioavailability and pharmacological properties.