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.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2024-11-06 DOI:10.1021/acs.biomac.4c01209

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

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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.

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由甲基丙烯酰明胶、羧甲基葡聚糖和透明质酸组成的博舒替尼负载纳米凝胶在结直肠癌控制给药中的 pH 反应性和聚合稳定性比较研究：广泛的体外研究

本研究调查了在结肠癌治疗中使用 pH 响应纳米凝胶递送博舒替尼（BOSU）的情况。纳米凝胶由三种聚合物配制而成：透明质酸（HA）、羧甲基葡聚糖（CMD）和甲基丙烯酰明胶（GelMA）。这些纳米凝胶通过与 BOSU 进行聚合物混合，然后进行 EDC/NHS 交联和超声处理，实现了较高的药物包埋效率（80-90%）。纳米凝胶非常稳定，ZETA电位为负（-20 至 -30 mV），粒径在 100 至 200 nm 之间。傅立叶变换红外分析证实了 GelMA 纳米凝胶中甲基丙烯酸酯化的成功。与正常 pH 值（7.4）下较慢的释放速度相比，在 pH 值为 5.0 时可观察到类似肿瘤环境的持续 BOSU 释放。细胞毒性测试表明，在较高剂量下，HCT116 结肠癌细胞的存活率降低了 70-80%，GelMA-BOSU 纳米凝胶明显减少了细胞迁移。在小鸡绒毛膜模型中证实了抗血管生成的效果，突出了这些纳米凝胶在结肠癌治疗中靶向输送 BOSU 的潜力。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.