Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Pakistan.
College of Pharmacy, University of Sargodha, Sargodha, Pakistan.
Drug Dev Ind Pharm. 2020 Feb;46(2):272-282. doi: 10.1080/03639045.2020.1716378. Epub 2020 Jan 22.
The study aimed to develop safe, effective, and targeted drug delivery system for administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in the form of microgels. We developed pH responsive microgels to overcome the mucosal damage caused by traditional immediate release dosage forms. Colon targeting and controlled release formulations have the potential to improve efficacy and reduce undesirable effects associated with NSAIDs. The pH sensitive oral hydrogel demonstrates the potential to target the colon. Cellulose acetate phthalate (CAP) and hydroxyethyl methacrylate (HEMA) based microgel particles were produced using a free radical polymerization technique using ammonium persulfate (APS) initiator and methylenebisacrylamide (MBA) as the crosslinking agent. Swelling and drug release studies were performed at a range of pH conditions. The produced formulations were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), and X-ray diffraction. Biocompatibility of the microgels was analyzed in cytotoxicity studies. The swelling and release rate were negligible at pH 1.2, which confirmed the pH-responsiveness of CAP--poly(HEMA). The co-polymeric system prevents the release of ketoprofen sodium in the stomach owing to limited swelling at gastric pH, whilst promoting release at the basic pH observed in the colon. SEM images confirmed porous nature of the microgels that facilitate effective drug diffusion through the polymeric matrix. Cytotoxicity studies revealed biocompatibility of hydrogels. These investigations showed that that the controlled drug release and gastro-protective drug delivery of NSAIDS was achieved using CAP--poly(HEMA) microgel particles.
本研究旨在开发安全、有效且靶向的药物传递系统，以微凝胶的形式给予非甾体抗炎药（NSAIDs）。我们开发了 pH 响应性微凝胶，以克服传统即刻释放剂型引起的粘膜损伤。结肠靶向和控释制剂有可能提高疗效并减少与 NSAIDs 相关的不良作用。pH 敏感的口服水凝胶显示出靶向结肠的潜力。使用过硫酸铵（APS）引发剂和亚甲基双丙烯酰胺（MBA）作为交联剂，通过自由基聚合技术制备了基于醋酸纤维素邻苯二甲酸酯（CAP）和羟乙基甲基丙烯酸酯（HEMA）的微凝胶颗粒。在一系列 pH 条件下进行了溶胀和药物释放研究。使用傅里叶变换红外光谱、热重分析、差示扫描量热法、扫描电子显微镜（SEM）和 X 射线衍射对所制备的配方进行了表征。通过细胞毒性研究分析了微凝胶的生物相容性。在 pH 1.2 时，溶胀和释放速率可以忽略不计，这证实了 CAP-聚（HEMA）的 pH 响应性。由于在胃 pH 下有限的溶胀，共聚物系统防止了酮洛芬钠在胃中的释放，而在结肠中观察到的碱性 pH 下促进了释放。SEM 图像证实了微凝胶的多孔性质，这有利于药物通过聚合物基质的有效扩散。细胞毒性研究表明水凝胶具有生物相容性。这些研究表明，使用 CAP-聚（HEMA）微凝胶颗粒实现了 NSAIDs 的控释和胃保护药物传递。
