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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. [ABSTRACT FROM AUTHOR]

pH-responsive nanogels have played an increasingly momentous role in tumor treatment. The focus of this study is to design and develop pH-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for the controlled release of doxorubicin hydrochloride (DOX) while enhancing its hydrophilicity. BIMIXHAC is crosslinked with carboxymethyl chitosan (CMC), hyaluronic acid sodium salt (HA), and sodium alginates (SA) using an ion crosslinking method. The chemical structure of chitosan derivatives was verified by 1H NMR and FT-IR techniques. Compared to hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-based nanogels, BIMIXHAC-based nanogels exhibit better drug encapsulation efficiency and loading capacity (BIMIXHAC-D-HA 91.76 %, and 32.23 %), with pH-responsive release profiles and accelerated release in vitro. The series of nanogels formed by crosslinking with three different polyanionic crosslinkers have different particle size potentials and antioxidant properties. BIMIXHAC-HA, BIMIXHAC-SA and BIMIXHAC-CMC demonstrate favorable antioxidant capability. In addition, cytotoxicity tests showed that BIMIXHAC-based nanogels have high biocompatibility. BIMIXHAC-based nanogels exhibit preferable anticancer effects on MCF-7 and A549 cells. Furthermore, the BIMIXHAC-D-HA nanogel was 2.62 times less toxic than DOX to L929 cells. These results suggest that BIMIXHAC-based nanogels can serve as pH-responsive nanoplatforms for the delivery of anticancer drugs. [ABSTRACT FROM AUTHOR]