Optimization of the Redox-Sensitive Doxorubicin Loaded Chitosan-based Nanoparticles by Box–Behnken Experimental Design

Abstract

Abstract Background Developing a satisfactory approach for delivering the chemotherapeutic drugs is one of the critical points in cancer treatment. Box–Behnken Design (BBD) is a Response Surface Methodology (RSM) that investigates the significant effects of various independent factors on dependent variables and also covers all potential effects of their interactions only by three levels of each factor. Methods and Results In this study, a Crosslinked Chitosan-L-Cysteine (Cs-Cys)/Tripolyphosphate (TPP) Nanoparticles (Cs-CysNPs) was synthesized to load Doxorubicin (DOX) (Cs-CysNPs-DOX) into a polymeric matrix as a promising redox responsive NP for breast cancer treatment. A statistical optimization by BBD was employed to examine the effects of the essential variables (CS-Cys concentration, TPP concentration, and Cs-Cys/TPP ratio) to optimize the Entrapment Efficiency (EE%) as the dependent variable. The optimized formulations with high EE% were obtained at middle levels of Cs-Cys concentration (1.25 mg/ml), Cs-Cys/TPP ratio (6:1) and high levels of the TPP concentration. The optimized Cs-CysNPs-DOX showed enhanced EE% and Drug Loading (DL%) compared to CsNPs. Also, they had an average hydrodynamic size of 144.55 nm and a Polydispersity Index (PDI) of 0.262, which showed a resealable size with sufficient PDI. Also, the final formulation of NPs had a positive zeta potential, which caused the high stability of the suspension. Conclusions Consequently, the optimized Cs-Cys NPs could be investigated as a suitable carrier for DOX entrapment and delivery to breast cancer cells.