Department of Pharmaceutics, Krishna Institute of Pharmacy, Krishna Institute of Medical Sciences Deemed To Be University, Karad, Maharashtra, 415539, India.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India.
Drug Deliv Transl Res. 2020 Aug;10(4):1002-1018. doi: 10.1007/s13346-020-00776-7.
The objective of the present study was to develop a pH-sensitive drug delivery system by using polymethylmethacrylate-grafted gellan gum (PMMA-g-GG). PMMA-g-GG was synthesized by free radical polymerization reaction by using redox initiator ceric ammonium nitrate (CAN), and a series of graft copolymers were prepared with varying concentrations of methylmethacrylate (MMA) and CAN. Grafting parameters such as the percentage and efficiency of grafting were calculated, and the effect of monomer as well as initiator concentration was studied on the grafting yield. Optimization was done by one optimal response surface methodology. The batch with a better percentage grafting and grafting efficiency was selected and characterized by elemental analysis (CHN), FT-IR, DSC, PXRD, H-NMR, and SEM. Furthermore, acute oral toxicity study and histopathological analysis suggested non-toxic and biocompatible nature of the grafted gum. Metformin hydrochloride pellets were prepared using PMMA-g-GG, characterized in detail, and assessed for biocompatibility and efficacy. PMMA-g-GG-based formulation (M4) exhibited a pH-sensitive as well as sustained release of the drug over the period of 12 h and the release profile followed Peppas model. In vivo efficacy studies indicated a promising antidiabetic potential of the prepared formulation. Thus, PMMA-g-GG-based formulations can be implicated as novel drug delivery systems for facilitated antidiabetic therapy in the near future. Graphical abstract.
本研究的目的是通过使用聚甲基丙烯酸甲酯接枝结冷胶（PMMA-g-GG）来开发一种 pH 敏感的药物传递系统。PMMA-g-GG 通过使用氧化还原引发剂硝酸铈铵（CAN）的自由基聚合反应合成，并制备了一系列具有不同甲基丙烯酸甲酯（MMA）和 CAN 浓度的接枝共聚物。计算了接枝参数，如接枝百分比和接枝效率，并研究了单体和引发剂浓度对接枝产率的影响。通过单因素响应面法进行了优化。选择具有更好接枝百分比和接枝效率的批次，并通过元素分析（CHN）、傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）、粉末 X 射线衍射（PXRD）、氢核磁共振（H-NMR）和扫描电子显微镜（SEM）进行了表征。此外，急性口服毒性研究和组织病理学分析表明接枝胶具有无毒和生物相容性。使用 PMMA-g-GG 制备盐酸二甲双胍微丸，并进行详细表征，评估其生物相容性和疗效。PMMA-g-GG 基配方（M4）表现出 pH 敏感性和药物在 12 小时内的持续释放，释放曲线遵循 Peppas 模型。体内疗效研究表明，所制备的制剂具有有前途的抗糖尿病潜力。因此，PMMA-g-GG 基制剂可被认为是未来促进抗糖尿病治疗的新型药物传递系统。
