Formulation, Optimization and Evaluation of Enzyme/pH Dual-Responsive Zein Nanoparticles for Colon-Specific Delivery of 5-Fluorouracil
DOI:
https://doi.org/10.64149/J.Carcinog.24.7s.350-358Keywords:
Zein nanoparticles; 5-Fluorouracil; Colon-specific delivery; Enzyme-responsive; pH-responsive; Drug delivery; Colorectal cancerAbstract
Purpose: This study aimed to develop and characterize enzyme/pH dual-responsive zein nanoparticles (ZNPs) for the colon-specific delivery of 5-fluorouracil (5-FU), a chemotherapeutic agent, to enhance its therapeutic efficacy and reduce systemic toxicity in colorectal cancer treatment.
Methods: Zein nanoparticles were fabricated using an antisolvent precipitation method and subsequently loaded with 5-FU. A 3² full factorial design was employed to optimize key formulation parameters, including zein concentration and crosslinker concentration, on encapsulation efficiency and particle size. The dual-responsive release mechanism was investigated through in vitro drug release studies at varying pH conditions (pH 1.2, 6.8, and 7.4) and in the presence of colonic enzymes. Furthermore, the in vivo antitumor efficacy of the optimized 5-FU-loaded ZNPs was evaluated in a xenograft mouse model of colorectal cancer, assessing tumor volume changes and histopathological alterations in colon tissue.
Results: The optimized ZNPs exhibited high encapsulation efficiency and suitable particle size for colon targeting. In vitro release studies demonstrated minimal 5-FU release in acidic gastric conditions (pH 1.2) and the small intestine (pH 6.8), with a significant burst release observed at colonic pH (pH 7.4) and in the presence of colonic enzymes, confirming the dual-responsive nature. In vivo studies revealed that 5-FU-loaded ZNPs significantly inhibited tumor growth and improved therapeutic outcomes compared to free 5-FU, with reduced systemic side effects. Histopathological analysis confirmed the colon-specific delivery and localized therapeutic action.
Conclusion: The developed enzyme/pH dual-responsive zein nanoparticles represent a promising strategy for the targeted delivery of 5-FU to the colon, offering a potential approach to improve the treatment of colorectal cancer by enhancing drug accumulation at the disease site and minimizing adverse effects.
