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基于含羞草/榅桲籽胶共聚物(甲基丙烯酸酯)水凝胶的卡培他滨控释系统:模拟研究、表征和毒理学评价。

Mimosa/quince seed mucilage-co-poly (methacrylate) hydrogels for controlled delivery of capecitabine: Simulation studies, characterization and toxicological evaluation.

机构信息

Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan.

Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan; Department of Pharmacy, University of Chakwal, Chakwal 48800, Pakistan.

出版信息

Int J Biol Macromol. 2024 Aug;275(Pt 1):133468. doi: 10.1016/j.ijbiomac.2024.133468. Epub 2024 Jun 28.

DOI:10.1016/j.ijbiomac.2024.133468
PMID:38945341
Abstract

This research focused on developing pH-regulated intelligent networks using quince and mimosa seed mucilage through aqueous polymerization to sustain Capecitabine release while overcoming issues like short half-life, high dosing frequency, and low bioavailability. The resulting MSM/QSM-co-poly(MAA) hydrogel was evaluated for several parameters, including complex structure formation, stability, pH sensitivity, morphology, and elemental composition. FTIR, DSC, and TGA analyses confirmed the formation of a stable, complex cross-linked network, demonstrating excellent stability at elevated temperatures. SEM analysis revealed the hydrogels' smooth, fine texture with porous surfaces. PXRD and EDX results indicated the amorphous dispersion of Capecitabine within the network. The QMM9 formulation achieved an optimal Capecitabine loading of 87.17 %. The gel content of the developed formulations ranged from 65.21 % to 90.23 %. All formulations exhibited excellent swelling behavior, with ratios between 65.91 % and 91.93 % at alkaline pH. In vitro dissolution studies indicated that up to 98 % of Capecitabine was released after 24 h at pH 7.4, demonstrating the potential for sustained release. Furthermore, toxicological evaluation in healthy rabbits confirmed the system's safety, non-toxicity, and biocompatibility.

摘要

本研究专注于通过水相聚合开发使用榅桲和金合欢种子黏液的 pH 调节智能网络,以持续释放卡培他滨,同时克服半衰期短、高给药频率和低生物利用度等问题。所得到的 MSM/QSM-co-poly(MAA)水凝胶通过多种参数进行了评估,包括复杂结构的形成、稳定性、pH 敏感性、形态和元素组成。FTIR、DSC 和 TGA 分析证实了稳定的、复杂的交联网络的形成,表明在高温下具有优异的稳定性。SEM 分析显示水凝胶具有光滑、精细的质地和多孔表面。PXRD 和 EDX 结果表明卡培他滨在网络中呈无定形分散。QMM9 制剂实现了 87.17%的最佳卡培他滨负载量。所开发制剂的凝胶含量范围为 65.21%至 90.23%。所有制剂均表现出优异的溶胀行为,在碱性 pH 下的比值在 65.91%至 91.93%之间。体外溶解研究表明,在 pH 7.4 下 24 小时后,高达 98%的卡培他滨被释放,显示出持续释放的潜力。此外,在健康兔中的毒理学评价证实了该系统的安全性、无毒性和生物相容性。

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