Aslam Aysha, Ashraf Muhammad Umer, Barkat Kashif, Mahmood Asif, Hussain Muhammad Ajaz, Farid-Ul-Haq Muhammad, Lashkar Manar O, Gad Heba A
Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan.
Department of Pharmacy, University of Chakwal, Chakwal 48800, Pakistan.
Pharmaceutics. 2023 Feb 15;15(2):650. doi: 10.3390/pharmaceutics15020650.
Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol-gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63-75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen-Crowell's kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.
采用自由基聚合技术制备了一种用于阿昔洛韦钠控释的刺激响应型智能木瓜/粘蛋白共聚（甲基丙烯酸酯）水凝胶。使用不同参数对所制备的水凝胶基质进行评估，如载药量（%）、溶胀动力学、pH和电解质响应性溶胀以及溶胶-凝胶分数。进行了药物-辅料相容性研究、扫描电子显微镜、热分析、粉末X射线衍射（PXRD）分析、体外药物释放研究、药物释放动力学和急性口服毒性研究。载药量结果显示不同制剂中阿昔洛韦钠的载药量为63 - 75%。水凝胶圆盘表现出pH响应性溶胀行为，在pH为7.4的磷酸盐缓冲液中溶胀最大，但在pH为1.2的酸性缓冲液中溶胀可忽略不计。所制备的水凝胶圆盘的溶胀动力学表现为二级动力学。此外，水凝胶圆盘对电解质（CaCl和NaCl）浓度有响应。傅里叶变换红外光谱（FTIR）结果证实通过自由基聚合形成了水凝胶。然而，阿昔洛韦的主要峰保持完整，证明了药物-辅料相容性。扫描电子显微镜（SEM）分析结果显示水凝胶圆盘表面多孔、粗糙，有多个裂缝和孔隙。粉末X射线衍射（PXRD）结果揭示了所制备水凝胶的无定形性质。溶出度研究表明在酸性环境中释放少量阿昔洛韦钠，而在磷酸盐缓冲液中观察到长达36小时的缓释。药物释放遵循Hixen-Crowell动力学和菲克扩散机制。毒性研究表明聚合物载体系统无毒。因此，这些结果表明木瓜/粘蛋白共聚（甲基丙烯酸酯）水凝胶是一种有潜力将阿昔洛韦长时间递送至肠道的智能材料。
