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<p>Developing a satisfactory approach to delivering 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 covers all potential effects of their interactions by only three levels of each factor. In this study, a crosslinked chitosan–L-cysteine (Cs–Cys)/tripolyphosphate (TPP) nanoparticle (Cs–CysNP) was synthesized to load doxorubicin (DOX; Cs–CysNPs-DOX) into a polymeric matrix as a promising redox-responsive nanoparticle 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 medium 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 with 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 an adequate PDI. Also, the final formulation of NPs had a positive zeta potential, which caused the high stability of the suspension. Consequently, the optimized Cs–CysNPs could be investigated as a suitable carrier for DOX entrapment and delivery to breast cancer cells.</p>

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

  • 期刊论文

  • 发表日期：

    2026年2月1日

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  • Mahsa Babaei,
  • Soheila Kashanian,
  • Zahra Salemi

摘要

Developing a satisfactory approach to delivering 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 covers all potential effects of their interactions by only three levels of each factor. In this study, a crosslinked chitosan–L-cysteine (Cs–Cys)/tripolyphosphate (TPP) nanoparticle (Cs–CysNP) was synthesized to load doxorubicin (DOX; Cs–CysNPs-DOX) into a polymeric matrix as a promising redox-responsive nanoparticle 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 medium 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 with 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 an adequate PDI. Also, the final formulation of NPs had a positive zeta potential, which caused the high stability of the suspension. Consequently, the optimized Cs–CysNPs could be investigated as a suitable carrier for DOX entrapment and delivery to breast cancer cells.