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用于结直肠癌控释给药的含甲基丙烯酰化明胶、羧甲基葡聚糖和透明质酸的博舒替尼纳米凝胶的pH响应性和聚集稳定性的比较研究:一项广泛的体外研究

Comparative Study of pH-Responsive and Aggregation Stability of Bosutinib-Loaded Nanogels Comprising Gelatin Methacryloyl, Carboxymethyl Dextran, and Hyaluronic Acid for Controlled Drug Delivery in Colorectal Cancer: An Extensive In Vitro Investigation.

作者信息

Bhattacharya Sankha, Bagade Shashikant, Sangave Preeti Chidambar, Kumar Devendra, Shaik Imran, Mukherjee Dhrubojyoti

机构信息

School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India.

出版信息

Biomacromolecules. 2024 Dec 9;25(12):7926-7950. doi: 10.1021/acs.biomac.4c01209. Epub 2024 Nov 6.

Abstract

This study investigates the use of pH-responsive nanogels for delivering Bosutinib (BOSU) in colon cancer treatment. Nanogels were formulated using three polymers: hyaluronic acid (HA), carboxymethyl dextran (CMD), and gelatin methacryloyl (GelMA). These nanogels achieved high drug entrapment efficiencies (80-90%) through polymer mixing with BOSU, followed by EDC/NHS cross-linking and sonication. The nanogels were stable, with negative zeta potentials (-20 to -30 mV) and particle sizes between 100 and 200 nm. Fourier-transform infrared analysis confirmed successful methacrylation in GelMA nanogels. Sustained BOSU release at pH 5.0 was observed, resembling tumor environments, compared to slower release at normal pH (7.4). Cytotoxicity tests showed 70-80% cell survival reduction in HCT116 colon cancer cells at higher doses, and GelMA-BOSU nanogels notably reduced cell migration. Antiangiogenic effects were confirmed in a chick chorioallantoic membrane model, highlighting the potential of these nanogels for targeted BOSU delivery in colon cancer therapy.

摘要

本研究调查了pH响应性纳米凝胶在结肠癌治疗中递送博舒替尼(BOSU)的应用。纳米凝胶由三种聚合物制备而成:透明质酸(HA)、羧甲基葡聚糖(CMD)和甲基丙烯酰化明胶(GelMA)。通过将聚合物与BOSU混合,然后进行EDC/NHS交联和超声处理,这些纳米凝胶实现了较高的药物包封率(80 - 90%)。纳米凝胶具有稳定性,zeta电位为负(-20至-30 mV),粒径在100至200 nm之间。傅里叶变换红外分析证实了GelMA纳米凝胶中甲基丙烯酰化反应成功。与在正常pH值(7.4)下较慢释放相比,在pH 5.0时观察到BOSU持续释放,类似于肿瘤环境。细胞毒性试验表明,在较高剂量下,HCT116结肠癌细胞的细胞存活率降低了70 - 80%,并且GelMA - BOSU纳米凝胶显著降低了细胞迁移。在鸡胚绒毛尿囊膜模型中证实了抗血管生成作用,突出了这些纳米凝胶在结肠癌治疗中靶向递送BOSU的潜力。

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