Sustained delivery of gemcitabine injectable mussel-inspired hydrogels for the local therapy of pancreatic cancer.

The issue of pervasively enhanced drug resistance of pancreatic cancer is fundamental to a better understanding of gemcitabine-based chemotherapy. Currently available treatment plans involving injectable therapeutics are mainly engineered to improve the performance and broaden their applications in the domain of biomedicine. Fixed-dose-rate infusion of free gemcitabine (Gem) has drawn appropriate attention for its potent anti-tumor efficacy against various solid tumors, whereas it remains a considerable challenge to extend its application and achieve better treatment. Here, we have prepared and demonstrated a long-acting delivery system using gemcitabine and injectable hydrogel for the localized treatment of pancreatic cancer. The hydrogel was prepared using polysaccharide derivatives, oxidized-carboxymethylcellulose (OCMC) and carboxymethylchitosan (CMCS) at optimal ratios by a dopamine-functionalized method for the controlled release of Gem. drug release behaviors for up to a week indicated sustained drug release of the Gem delivery system. Moreover, desirable apoptosis promotion and apparent cellular proliferation inhibition associated with the drug depot have been found against BxPC-3 pancreatic cancer cells, bringing minimized side effects to systemic normal tissues. The current findings manifested that the release out of the localized delivery platform in a sustained pattern afforded a durable gemcitabine-based chemotherapy effect and inhibited tumor metastasis more persistently after intratumoral injection of the Gem@Gel system, thereby advancing the development of novel drug-loaded materials with properties not accessed previously.