Abstract P4-10-30: Injectable novel hydrogel formulation for bacterial encapsulation

Abstract Background information: Nowadays, temperature-sensitive hydrogels are widely used for the targeted delivery of drugs to solid tumor sites, as they can become solid at body temperature and retain drugs only at the tumor site. They are biodegradable, biocompatible, and have pores for the sustained release of drugs, which makes them perfect scaffolds for trapping bacterial cells. Mesoporous hydrogel with genetically engineered bacteria that synthesizes anticancer drugs inside can be injected into subcutaneous levels of the human body to kill rapidly differentiating cancer cells. We synthesized a chitosan-β-glycerophosphate-hyaluronic acid hydrogel, which was then encapsulated with genetically engineered E. coli bacteria. The main goal of this study was to create a scaffold for genetically engineered bacteria and assess its effectiveness regarding pore size, release behavior, and cytotoxic activity. Methods: Chitosan-β-glycerophosphate-HA hydrogel was synthesized via physical crosslinking and sol-gel transition was examined using rheometer. SEM imaging showed correlation between pore size and concentration of hyaluronic acid. MTT assay assessed cytotoxicity levels towards E.coli cells and release was monitored via Bacterial Release Test. Results: Sol-gel transition appeared in 8 min and the rheometer identified solidification temperature as 36.62 °C. With increasing concentrations of hyaluronic acid from 0.5% to 2%, the pore size decreases from 56 um to 3.94 um. Viability of E.coli cells reduced to 20.9045% which indicates that hydrogel does not have significant adverse effects on bacterial cells. Release in 72 hours showed sustained release bacteria, which confirmed that hydrogel can be used as a drug delivery system. Conclusion: Novel temperature sensitive drug delivery systems for bacterial encapsulation can be time and resource saving for drugs released by bacterial strains, chitosan-β-glycerophosphate-hyaluronic acid hydrogel characterizations showed stronger ability to be used as scaffold and further in-vivo studies are needed. Citation Format: Makpal Akishova, Ansal Diassova, Arailym Myrzagaliyeva, Yernur Kenzhegazin, Irshad Kammakakam. Injectable novel hydrogel formulation for bacterial encapsulation [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-10-30.