State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
J Mater Chem B. 2022 Aug 24;10(33):6338-6350. doi: 10.1039/d1tb02858h.
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.
普遍增强的胰腺癌耐药性问题对于更好地理解吉西他滨为基础的化疗至关重要。目前可用的涉及注射治疗的治疗方案主要是为了提高其性能并拓宽其在生物医学领域的应用而设计的。游离吉西他滨（Gem）的固定剂量率输注因其对各种实体瘤的强大抗肿瘤功效而引起了适当的关注，然而，要将其应用扩展并实现更好的治疗效果仍然是一个相当大的挑战。在这里，我们使用吉西他滨和可注射水凝胶制备并展示了一种长效递药系统，用于局部治疗胰腺癌。该水凝胶是通过多巴胺功能化方法，以最佳比例使用多糖衍生物氧化羧甲基纤维素（OCMC）和羧甲基壳聚糖（CMCS）制备的，用于 Gem 的控制释放。长达一周的药物释放行为表明 Gem 递药系统具有持续的药物释放。此外，与药物库相关的令人满意的促凋亡和明显的细胞增殖抑制作用已被发现对 BxPC-3 胰腺癌细胞具有作用，从而将全身正常组织的副作用降至最低。目前的研究结果表明，局部递药平台以持续模式释放药物可提供持久的基于吉西他滨的化疗效果，并在瘤内注射 Gem@Gel 系统后更持久地抑制肿瘤转移，从而推进具有以前无法获得的特性的新型载药材料的发展。
