Department of Pharmaceutics, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra state, India.
Department of Pharmaceutics, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra state, India.
Int J Biol Macromol. 2023 Mar 1;230:123360. doi: 10.1016/j.ijbiomac.2023.123360. Epub 2023 Jan 27.
Microwave-assisted grafting of polyacrylamide on sesbania gum (PAAM-g-SG) was implemented employing a 3 full factorial experimental design and was hydrolyzed using sodium hydroxide (NaOH) to form H-PAAM-g-SG. Further, the diclofenac sodium-loaded novel pH-sensitive interpenetrating polymeric network (IPN) microbeads were designed using an optimized H-PAAM-g-SG and sodium alginate (SA). Different spectroscopic analysis including FTIR spectroscopy, H NMR spectroscopy, elemental analysis, thermal analysis, etc. was performed to confirm the synthesis of PAAM-g-SG and diclofenac-loaded pH-sensitive IPN H-PAAM-g-SG-SA microbeads. Here, Ca ions combine with two strands of SA and form a round-shape structure that encloses uncross-linked H-PAAM-g-SG polymer and diclofenac sodium. As well, glutaraldehyde (GL) addition improved the mechanical strength due to acetal structure between hydroxyl of H-PAAM-g-SG and aldehyde of GL. The drug entrapment was confirmed proportional relationship to the Ca ions concentration whereas an increase in GL concentration resulted in a reduced drug entrapment. The pH pulsatile study assured the reversible swelling-shrinkage behavior of IPN microbeads due to the carboxyl group of PAAM-g-SG. The drug release from H-PAAM-g-SG-SA microbeads (batch: S9) was found to be 84.21 % (12h) which was non-significant (p > 0.05; f2 = 79 ∼ 90) over marketed formulation (83.31 %). Moreover, it follows the Korsmeyer Peppas (R = 0.996) as the best-fit release kinetic model. The pH-sensitive release of diclofenac sodium from IPN H-PAAM-g-SG-SA microbeads was assured based on in vivo anti-inflammatory activity (p < 0.05). Therefore, developed novel pH-sensitive IPN microbeads based on H-PAAM-g-SG are a promising polymeric carrier substitute for delivery of drugs actuated by a pH stimulus.
采用 3 全因子实验设计，实现了微波辅助丙烯酰胺接枝田菁胶（PAAM-g-SG），并用氢氧化钠（NaOH）水解形成 H-PAAM-g-SG。进一步，使用优化的 H-PAAM-g-SG 和海藻酸钠（SA）设计了载有双氯芬酸钠的新型 pH 敏感互穿聚合物网络（IPN）微球。进行了不同的光谱分析，包括傅里叶变换红外光谱（FTIR）、核磁共振光谱（H NMR）、元素分析、热分析等，以确认 PAAM-g-SG 和载有双氯芬酸钠的 pH 敏感 IPN H-PAAM-g-SG-SA 微球的合成。在这里，Ca 离子与两条 SA 链结合，形成圆形结构，包围未交联的 H-PAAM-g-SG 聚合物和双氯芬酸钠。此外，戊二醛（GL）的加入由于 H-PAAM-g-SG 的羟基和 GL 的醛基之间的缩醛结构提高了机械强度。药物包封率与 Ca 离子浓度呈比例关系，而 GL 浓度的增加导致药物包封率降低。pH 脉冲研究确保了 IPN 微球的可逆溶胀-收缩行为，这是由于 PAAM-g-SG 的羧基。从 H-PAAM-g-SG-SA 微球（批次：S9）中释放药物的研究发现，在 12 小时内，药物释放率为 84.21%（p>0.05；f2=79~90），与市售制剂（83.31%）无显著差异。此外，它遵循 Korsmeyer-Peppas（R=0.996）作为最佳拟合释放动力学模型。基于体内抗炎活性（p<0.05），证实了载有双氯芬酸钠的 IPN H-PAAM-g-SG-SA 微球的 pH 敏感释放。因此，基于 H-PAAM-g-SG 的新型 pH 敏感 IPN 微球是一种有前途的聚合物载体替代品，可用于输送 pH 刺激驱动的药物。
