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水飞蓟素种子黏胶/β-环糊精/蒙脱土-钠-接枝-共聚(甲基丙烯酸酯)基 pH 敏感型聚合物载体用于卡培他滨的控制释放。

Quince seed mucilage/β-cyclodextrin/Mmt-Na-co-poly (methacrylate) based pH-sensitive polymeric carriers for controlled delivery of Capecitabine.

机构信息

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

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

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 4):127032. doi: 10.1016/j.ijbiomac.2023.127032. Epub 2023 Sep 22.

Abstract

In current work, quince seed mucilage and β-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system's stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %-93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine. Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t (10.57 h), AUC (121.52 μg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system's safety, non-toxicity, and biocompatibility.

摘要

在当前的工作中,使用水溶液自由基聚合开发了榅桲籽胶和β-环糊精基 pH 调节水凝胶,以维持卡培他滨的释放模式并克服其缺点,如高剂量频率、半衰期短和生物利用度低。开发的网络进行了热分析、傅里叶变换红外光谱、粉末 X 射线衍射、元素分析、扫描电子显微镜、平衡溶胀和体外释放研究,以评估网络系统的稳定性、络合、形态和 pH 响应。形成了热稳定的 pH 响应交联网络。通过将含有卡培他滨的粘土掺入溶胀水凝胶中制备纳米复合水凝胶。所有配方在 pH 7.4 时的平衡溶胀率均在 67.98%-92.98%之间。在水凝胶的情况下,观察到最佳的卡培他滨负载(88.17%),而在纳米复合水凝胶中为 74.27%。在开发的配方中观察到优异的凝胶含量(65.88%-93.56%)。元素分析确保了卡培他滨的成功掺入。纳米复合水凝胶在 30 小时后释放 80.02%的药物时间更长。在口服药代动力学中,NC 水凝胶的 t(10.57 小时)、AUC(121.52μg.h/ml)和 MRT(18.95 小时)均高于水凝胶。这些发现表明,pH 响应载体系统可以提高卡培他滨的疗效并减少癌症治疗中的给药频率。毒性分析证明了该系统的安全性、无毒性和生物相容性。

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