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 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2024-11-06 DOI:10.1021/acs.biomac.4c0120910.1021/acs.biomac.4c01209

Sankha Bhattacharya*, Shashikant Bagade, Preeti Chidambar Sangave, Devendra Kumar, Imran Shaik and 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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由明胶、甲基丙烯酰、羧甲基葡聚糖和透明质酸组成的博苏替尼负载纳米凝胶用于结直肠癌药物递送的ph响应和聚集稳定性的比较研究：一项广泛的体外研究

本研究探讨了ph反应纳米凝胶在结肠癌治疗中递送博舒替尼的应用。纳米凝胶采用三种聚合物配制：透明质酸（HA）、羧甲基葡聚糖（CMD）和明胶甲基丙烯酰（GelMA）。通过将聚合物与BOSU混合，然后进行EDC/NHS交联和超声处理，这些纳米凝胶获得了很高的药物包裹效率（80-90%）。纳米凝胶稳定，zeta电位为负（- 20 ~ - 30 mV），粒径在100 ~ 200 nm之间。傅里叶变换红外分析证实了GelMA纳米凝胶的甲基丙烯酸化成功。在pH 5.0时观察到BOSU的持续释放，类似于肿瘤环境，而在正常pH（7.4）下释放较慢。细胞毒性试验显示，高剂量的HCT116结肠癌细胞存活率降低70-80%，GelMA-BOSU纳米凝胶显著降低细胞迁移。在鸡绒毛膜尿囊膜模型中证实了抗血管生成作用，强调了这些纳米凝胶在结肠癌治疗中靶向BOSU递送的潜力。

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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.