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(β-环糊精-甲基丙烯酸)/钠基蒙脱土纳米复合水凝胶的制备及其用于洛伐他汀控制释放的体外评价。

Development and in vitro evaluation of (β-cyclodextrin-g-methacrylic acid)/Na-montmorillonite nanocomposite hydrogels for controlled delivery of lovastatin.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan.

Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad, Pakistan.

出版信息

Int J Nanomedicine. 2019 Jul 17;14:5397-5413. doi: 10.2147/IJN.S209662. eCollection 2019.

Abstract

Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage.  It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. The objective of this study was to prepare and optimize nontoxic, biocompatible β-CD-g-MAA/Na-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. β-CD-g-MAA/Na-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using  β-CD  as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R and value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. A novel pH responsive crosslinked network containing β-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.

摘要

高脂血症是指低密度脂蛋白水平升高,导致脂肪在动脉中沉积、硬化和阻塞。它是高血压、心血管疾病、糖尿病等多种危及生命的病理状况的主要原因。本研究的目的是制备和优化具有不同聚合物、单体和蒙脱土含量的无毒、生物相容的β-CD-g-MAA/Na-MMT 纳米复合水凝胶。此外,还测定并比较了其降低血脂的潜力与其他方法。通过自由基聚合,用β-CD 作为聚合物、MAA 作为单体、MBA 作为交联剂、蒙脱土作为粘土,制备了β-CD-g-MAA/Na-MMT 纳米复合水凝胶(BM-1 至 BM9)。对所开发的网络进行了 FTIR、DSC、TGA、PXRD、SEM、溶胶-凝胶分数(%)、溶胀研究、抗高血脂研究和毒性研究。在较高的 pH 值下,获得了最佳的溶胀(94.24%)和释放(93.16%)。根据 R 和 值,LVT 释放遵循零级动力学,分别具有超案例 II 型传输释放机制。拉伸强度和断裂伸长率分别为 0.0283MPa 和 94.68%。凝胶分数在 80.55-98.16%之间。抗高血脂研究表明,LDL 水平从 522.24±21.88mg/dl 显著降低至 147.63±31.5mg/dl。毒性研究保证了所开发网络的安全性。本研究开发并优化了一种含有β-CD-g-聚(甲基丙烯酸)聚合物和 MMT 的新型 pH 响应交联网络,具有优异的机械性能、溶胀性能和释放性能以及降低血脂的潜力。

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