Department of Pharmacy, The University of Lahore, Gujrat Campus, Pakistan.
Department of Pharmacy, Quid-i-Azam University Islamabad, Pakistan.
Carbohydr Polym. 2021 Apr 1;257:117617. doi: 10.1016/j.carbpol.2021.117617. Epub 2021 Jan 16.
Current work focuses on the synthesis and characterization of novel pH-sensitive biocompatible gelatin/carboxymethyl cellulose based hydrogels by free radical polymerization technique cross-linked with glutaraldehyde. Effect of pH, polymer ratio and variable crosslinking concentrations on dynamic swelling, equilibrium swelling, porosity, sol-gel analysis and in vitro release pattern was investigated. Hydrogel structure was confirmed by FTIR, XRD, and DSC. Moreover scanning electron microscopy confirmed the porous structure of gel network. Various structure property relationships like average molecular weight between crosslinks (Mc), solvent interaction parameters, volume fraction of polymer (V) and diffusion coefficient (D) that affect the release behaviour were determined. Results showed that maximum swelling and highest release of drug occurred at pH 1.2. Porosity and gel fraction increased by increasing polymer load. The invivo absorption and pharmacokinetics evaluation in rabbit's models revealed the controlled nature of hydrogels. MTT assay confirmed the biocompatible nature of blank hydrogels against Vero cell lines and cytotoxic potential against HeLa cell lines. The preliminary safety evaluation and oral tolerability revealed that the hydrogel solution is safe up to 4000 mg/kg body weight without causing any hematological or histopathological changes in rabbits.
目前的工作重点是通过自由基聚合技术合成和表征新型 pH 敏感的生物相容性明胶/羧甲基纤维素水凝胶，该水凝胶通过戊二醛交联。研究了 pH 值、聚合物比例和不同交联浓度对动态溶胀、平衡溶胀、孔隙率、溶胶-凝胶分析和体外释放模式的影响。通过傅里叶变换红外光谱（FTIR）、X 射线衍射（XRD）和差示扫描量热法（DSC）确认了水凝胶的结构。此外，扫描电子显微镜（SEM）证实了凝胶网络的多孔结构。确定了影响释放行为的各种结构性能关系，如平均交联分子量（Mc）、溶剂相互作用参数、聚合物体积分数（V）和扩散系数（D）。结果表明，在 pH 值为 1.2 时，水凝胶的溶胀率和药物释放率最高。随着聚合物负载的增加，孔隙率和凝胶分数增加。在兔模型中的体内吸收和药代动力学评估表明了水凝胶的控制释放特性。MTT 测定证实了空白水凝胶对 Vero 细胞系的生物相容性，以及对 HeLa 细胞系的细胞毒性潜力。初步的安全性评价和口服耐受性研究表明，水凝胶溶液在高达 4000mg/kg 体重的剂量下是安全的，不会导致兔子出现任何血液学或组织病理学变化。
