Sustained delivery of gemcitabine via in situ injectable mussel-inspired hydrogels for the local therapy of pancreatic cancer. Issue 33 (5th August 2022)

• Record Type: Journal Article
• Authors: Xu, Li; Tang, Shengnan; Yang, Huiquan; Liang, Min; Ren, Pengfei; Wei, Dandan; He, Jian; Kong, Weiwei; Liu, Peidang; Zhang, Tianzhu
• Is Part Of: Journal of materials chemistry. Volume 10:Issue 33(2022)
• Page Start: 6338
• Page End: 6350
• Publication Date: 2022-08-05
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d1tb02858h
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : A desirable therapeutic strategy has been designed and optimized for the localized drug delivery system in vitro and in vivo against pancreatic cancer cells, having the highest possible deceleration of tumor growth with the minimum use of doses. Abstract : 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 in situ 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. In vitro 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 in vitro 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.