Combination of gemcitabine and rapamycin in a polymeric thermogel for targeted treatment of metastatic pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) has a fatal prognosis. Conventional intravenous chemotherapy agents have limitations due to low tumor tissue delivery efficiency and high systemic toxicity. Therefore, intraperitoneal drug delivery systems that can maximize the therapeutic effect of chemotherapeutic agents while minimizing systemic toxicity are gaining attention. This study developed a temperature-sensitive PLGA-PEG-PLGA hydrogel loaded with gemcitabine (GEM) and rapamycin (RAPA) to propose a local anticancer therapy strategy through intraperitoneal injection. The synergistic effects of the two drugs at various molar ratios were evaluated, and the hydrogel with a GEM:RAPA ratio of 11:1 (g(GR)) demonstrated optimal anticancer activity. In cytotoxicity experiments using a Panc-1-luc2 tumor spheroid model, the g(GR)-treated group showed a 2.75-fold higher cell growth inhibition rate relative to the control group. Additionally, in in vivo drug release experiments in mice, GEM was released more rapidly than RAPA, and the hydrogel was completely degraded within 48 hours, which was similar to the in vitro release pattern. In vivo studies, g(GR) showed significant tumor growth inhibition and low toxicity highlighting its potential as an intraperitoneal drug delivery system. This study will developing temperature-sensitive hydrogel for localized drug delivery and assist data for future clinical administering.
2025 Spring Convention