This study was aimed to develop novel in situ forming gels based on N-vinylcaprolactam, sodium alginate, and N,N-methylenebisacrylamide. The in situ Poly (NVRCL-g-NaAlg) gels were developed using the cold and free radical polymerization method. The structure formation, thermal stability, and porous nature of gels was confirmed by FTIR, NMR, DSC, TGA, and SEM. The tunable gelation temperature was evaluated by tube titling and rheological analysis. Optical transmittance showed that all formulations demonstrated phase transition around 33 °C. The swelling and release profile showed that gels offered maximum swelling and controlled 5-FU release at 25 °C and pH (7.4), owing to a relaxed state. Porosity and mesh size showed an effect on swelling and drug release. The in vitro degradation profile demonstrated a controlled degradation rate. An MTT assay confirmed that formulations are safe tested against Vero cells. In vitro cytotoxicity showed that 5-FU loaded gels have controlled cytotoxic potential against HeLa and MCF-7 cells (IC₅₀ = 39.91 µg/mL and 46.82 µg/mL) compared to free 5-FU (IC₅₀ = 50.52 µg/mL and 53.58 µg/mL). Histopathological study demonstrated no harmful effects of gels on major organs. The in vivo bioavailability in rabbits showed a controlled release in gel form (C_max, 1433.59 ± 45.09 ng/mL) compared to a free drug (C_max, 2263.31 ± 13.36 ng/mL) after the subcutaneous injection.

中文翻译：

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基于聚（N-乙烯基己内酰胺接枝海藻酸钠）的可注射 pH/热响应原位形成储库水凝胶，用于延长受控抗癌药物输送；体外、体内表征和毒性评估


本研究旨在开发基于 N-乙烯基己内酰胺、海藻酸钠和 N,N-亚甲基双丙烯酰胺的新型原位形成凝胶。原位聚（NVRCL-g-NaAlg）凝胶是采用冷自由基聚合方法开发的。通过 FTIR、NMR、DSC、TGA 和 SEM 证实了凝胶的结构形成、热稳定性和多孔性质。通过管标题和流变分析评估可调凝胶化温度。透光率表明所有配方均在 33 °C 左右发生相变。溶胀和释放曲线表明，由于松弛状态，凝胶在 25 °C 和 pH (7.4) 下可实现最大溶胀并控制 5-FU 释放。孔隙率和网格尺寸对溶胀和药物释放有影响。体外降解曲线显示了受控的降解速率。 MTT 测定证实该制剂针对 Vero 细胞是安全的。体外细胞毒性表明_，与游离 5-FU（IC ₅₀ = 50.52 µg/mL 和53.58 微克/毫升）。组织病理学研究表明凝胶对主要器官没有有害影响。皮下注射后，与游离药物（C _max ，2263.31 ± 13.36 ng/mL）相比，兔子的体内生物利用度显示出凝胶形式的控释（C _max ，1433.59 ± 45.09 ng/mL）。