Abstract

The present study was undertaken to investigate the effect of the composition of the polymerization medium and the type of drug/drug loading process on the mechanical strengths and release profiles of poly(N-isopropylacrylamide-co-N-[3-(dimethylamino)propyl] methacrylamide) P(NIPAAm-co-DMAPMAAm) hydrogels. In line with this goal firstly, the temperature- and pH-responsive hydrogels of NIPAAm and DMAPMAAm were synthesized in three different media at 60 °C: pH 7.4 phosphate-buffered saline (PBS), pH 7.4 phosphate buffer without NaCl/KCl (PB), and distilled-deionized water (pH ≈ 5.5 DDW). The result is that the presence of anionic species such as phosphate (HPO₄^2-/H₂PO₄^-) and chloride (Cl^-) ions in the solution affects on their basic network properties such as volumetric swelling ratio and compression modulus. To evaluate their intermolecular interactions with protonated DMAPMAAm units and drug molecules, depending on composition, type of loading process and drug structure, each of the hydrogels was loaded with diclofenac sodium (DFNa) and theophylline (Thp) by using both diffusion and in situ loading methods. DFNa and Thp release profiles in pH 7.4 PBS at 37 °C were analysed by using zero-order, first-order, Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models. It has been observed that for the first 60% of DFNa and Thp releases from P(NIPAAm-co-DMAPMAAm) hydrogels synthesized in PB at 60 °C, the contribution of the chain relaxation for the copolymer hydrogels loaded during gelation process was higher than the ones loaded by diffusion process.

摘要

本研究旨在研究聚合介质的组成和药物/药物加载过程的类型对聚（N-异丙基丙烯酰胺-co-N-[3-（二甲氨基）丙基）机械强度和释放曲线的影响。 ] 甲基丙烯酰胺) P(NIPAAm-co-DMAPMAAm) 水凝胶。根据这一目标，NIPAAm 和 DMAPMAAm 的温度和 pH 响应水凝胶在 60 °C 下在三种不同的介质中合成：pH 7.4 磷酸盐缓冲盐水 (PBS)、pH 7.4 磷酸盐缓冲液，不含 NaCl/KCl (PB ) 和蒸馏去离子水 (pH ≈ 5.5 DDW)。结果是阴离子物质如磷酸盐 (HPO ₄ ^2- /H ₂ PO ₄ ^- ) 和氯化物 (Cl ^-) 溶液中的离子会影响它们的基本网络特性，例如体积溶胀比和压缩模量。为了评估它们与质子化 DMAPMAAm 单元和药物分子的分子间相互作用，根据组成、加载过程的类型和药物结构，每个水凝胶通过扩散和原位加载双氯芬酸钠 (DFNa) 和茶碱 (Thp)加载方法。通过使用零阶、一阶、Higuchi、Korsmeyer-Peppas 和 Peppas-Sahlin 模型分析 37 °C 下 pH 7.4 PBS 中的 DFNa 和 Thp 释放曲线。据观察，对于 60 °C 下 PB 中合成的 P(NIPAAm-co-DMAPMAAm) 水凝胶释放的前 60% DFNa 和 Thp，凝胶化过程中负载的共聚物水凝胶的链松弛贡献高于通过扩散过程加载的那些。