Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

Abstract

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier.