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用于抗疟疾药物口服递送的天然聚合物基水凝胶的制备及细胞毒性评估。

Preparation of natural polymer-based hydrogels for oral delivery of anti-malarial drug: and cytotoxicity evaluation.

作者信息

Suhail Muhammad, Wahab Abdul, Wang Guiyue, An Susu, Kiran Bushra, Jabeen Naila, Iqbal M Zubair, Kong Xiangdong, Wu Pao-Chu

机构信息

Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University Hangzhou 310018 China.

Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University Hangzhou 310018 China.

出版信息

RSC Adv. 2025 Aug 26;15(37):30378-30386. doi: 10.1039/d5ra04256a. eCollection 2025 Aug 22.

Abstract

The current investigation involved the fabrication of gelatin-based hydrogels for controlled delivery of quinine. Hence, pH-responsive and biocompatible hydrogels were developed using natural polymer gelatin and synthetic monomer acrylic acid. The drug-loaded hydrogels indicated a new carrier system, which was confirmed by various physicochemical characterizations, including FTIR, TGA, DSC, and XRD, whereas SEM revealed the morphology of unloaded and drug-loaded hydrogels, respectively. Similarly, sol-gel and porosity studies were conducted to assess the soluble, insoluble, and fluid penetration across the prepared network. A significant increase in gelation, whereas a decline in sol fraction was detected with high hydrogel contents. Unlike gel fraction, a decline was observed with high integration of gelatin and ','-methylene bisacrylamide, while acrylic acid showed the same effects as gel fraction on the porosity of the polymeric matrix. Swelling and drug release investigations confirmed the pH-dependent release of quinine at various simulated pH values of 1.2, 4.6, and 7.4, respectively. Both swelling and drug release showed a high swelling index and release of the drug from the fabricated hydrogel at higher pH values compared to lower pH values. Similarly, drug loading was conducted by a swelling and diffusion approach. The effects of acrylic acid, gelatin, and ','-methylene bisacrylamide were the same on swelling, drug loading, and release as porosity. The biodegradation study revealed that high polymer, monomer, and crosslinker concentrations led to a slow hydrogel degradation. Furthermore, the developed matrix was subjected to cytotoxicity and cell viability studies on mouse fibroblast L929 cells, which indicated safe utilization of polymeric hydrogels with negligible toxicity. Hence, the strategy of preparing pH-responsive hydrogels of gelatin facilitates the controlled delivery of quinine for a prolonged time in order to overcome the challenges of quinine generated after its multiple intakes.

摘要

当前的研究涉及制备用于控制递送奎宁的明胶基水凝胶。因此,使用天然聚合物明胶和合成单体丙烯酸开发了pH响应性和生物相容性水凝胶。载药水凝胶表明了一种新的载体系统,这通过包括傅里叶变换红外光谱(FTIR)、热重分析(TGA)、差示扫描量热法(DSC)和X射线衍射(XRD)在内的各种物理化学表征得到证实,而扫描电子显微镜(SEM)分别揭示了未载药和载药水凝胶的形态。同样,进行了溶胶 - 凝胶和孔隙率研究,以评估可溶性、不溶性以及流体在制备的网络中的渗透情况。随着水凝胶含量的增加,凝胶化显著增加,而溶胶分数下降。与凝胶分数不同,随着明胶和N,N'-亚甲基双丙烯酰胺的高整合度,观察到下降,而丙烯酸对聚合物基质的孔隙率表现出与凝胶分数相同的影响。溶胀和药物释放研究证实了奎宁在分别为1.2、4.6和7.4的各种模拟pH值下的pH依赖性释放。与较低pH值相比,溶胀和药物释放在较高pH值下均显示出较高的溶胀指数和药物从制备的水凝胶中的释放。同样,通过溶胀和扩散方法进行药物负载。丙烯酸、明胶和N,N'-亚甲基双丙烯酰胺对溶胀、药物负载和释放的影响与孔隙率相同。生物降解研究表明,高聚合物、单体和交联剂浓度导致水凝胶降解缓慢。此外,对所开发的基质进行了对小鼠成纤维细胞L929细胞的细胞毒性和细胞活力研究,结果表明聚合物水凝胶具有安全的利用率,毒性可忽略不计。因此,制备明胶pH响应性水凝胶的策略有助于长时间控制奎宁的递送,以克服多次摄入奎宁后产生的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b50/12379761/23301b6140ca/d5ra04256a-f1.jpg

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