In-situ Preparation of Zeolitic Imidazolate Framework-8 Modified Dialdehyde Starch-Crosslinked Chitosan Hydrogel Films as an Antibacterial Bio-platform for pH-sensitive Doxorubicin Delivery
摘要
Recently, hydrogel films, due to their biocompatibility, high drug and encapsulation efficacy, and adjustable physicochemical features, have emerged as promising candidates for delivering therapeutics in the treatment of human cancers. Therefore, this study aimed to design dialdehyde starch-crosslinked chitosan hydrogel films modified zeolitic imidazolate framework-8 (ZIF-8) for controlled release of doxorubicin (DOX) to HeLa cancer cells. For the preparation these hydrogel films, the dialdehyde starch (DS) in different percentages was utilized to crosslink chitosan (CS) through the Schiff base imine reaction, which 5% was chosen as the optimal content for preparing CS hydrogel films with higher swelling capacity (1000% at pH 7.4 for 72 h). Then, a subsequent in-situ synthesis method was employed to grow antibacterial ZIF-8 nanoparticles on the DS-CS hydrogel films (DS-CS/ZIF-8). To elucidate the effectiveness of the DS-CS/ZIF-8 nanocomposite hydrogel films as a pH-responsive drug carrier, DOX was loaded as a model anticancer drug (97.6%) by soaking in a solution of the drug. The in-vitro DOX release study indicated a time-dependent, pH-sensitive controlled release profile (< 35% at pH 7.4 and about 90% at pH 5 over 72 h). Notably, the MTT assay demonstrated good cytocompatibility and significant cytotoxicity against the HeLa cancer cells (cell viability < 50% at 6 µg/mL) for both the DS-CS/ZIF-8 and DOX-loaded DS-CS/ZIF-8. The DS-CS/ZIF-8 showed improved antibacterial properties toward both S. aureus (MIC: 31.2 µg•mL–1) and E. coli (MIC: 62.5 µg•mL–1) bacteria. Based on the obtained results, the synthesized biocompatible nanocomposite hydrogel films with pH-sensitive features have the potential for use as an implantable anticancer treatment.