Preparation, properties and drug controlled release mechanism of pH/salt dual-sensitive poly(ether-based imidazoles ionic liquid) gel

pH/盐双敏性聚醚基咪唑类离子液体凝胶的制备、性质及药物控释机制研究

¹ School of Environment and Chemical Engineering, Xi'an Polytechnic University, Xi'an 710600, China
² Research Institute of Shaanxi Yanchang Petroleum (Group) Co., Ltd., Xi'an 710061, China
³ School of Urban Planning and Engineering, Xi'an Polytechnic University, Xi'an 710600, China

Received: 9 June 2021

Abstract

Using N-vinylimidazole as the reactant and introducing different ether-based side chains pH/salt dual-sensitive poly(imidazole ionic liquid) gel (P[C_nOC₂vim]Cl, n=1, 2, 3) was designed and synthesized. The structure characteristic of the gel was determined by IR spectra and SEM. The swelling ratio of gel under different conditions was investigated, including releasing property for ciprofloxacin (CIP) and berberine (Ber). The results showed that P[C_nOC₂vim]Cl(n=1, 2, 3) gel exhibits typical pH-sensitivity and salt-sensitivity. Its swelling ratio increased first and then decreased, and reached the maximum when the value of pH was 7.4; the swelling rate is smaller under the higher concentration of the NaCl. Furthermore, P[COC₂vim]Cl gel with the short ether chain has the highest release rate of CIP and Ber at pH=7.4, the release behavior is in accord with the first-order kinetic equation. With the increase of the side chain of ether group, the cumulative release rate of P[C_nOC₂vim]Cl(n=2, 3) gel to CIP and Ber decreased obviously, and the behavior comforts to Higuchi kinetic equation. The results suggest that P[C_nOC₂vim]Cl(n=1, 2, 3) gel is the pH/salt dual-sensitive potential carrier for controlled drug release.

摘要

以N-乙烯基咪唑为反应物, 在咪唑环上引入不同醚基侧链, 设计合成了3种pH/盐双敏性聚醚基咪唑类离子液体凝胶(P[C_nOC₂vim]Cl, n=1, 2, 3)。用红外光谱、扫描电镜表征了其结构特征, 测试了不同条件下凝胶的溶胀性能, 并研究了凝胶对药物环丙沙星(CIP)、黄连素(Ber)的缓释效果。结果表明, P[C_nOC₂vim]Cl(n=1, 2, 3)凝胶具有明显的pH和盐敏感性, pH升高, 溶胀率先增大后减小, 在pH为7.4时达到最大; NaCl浓度越高, 溶胀率越小。短醚基链P[COC₂vim]Cl凝胶在pH=7.4模拟肠液环境中CIP、Ber释放率最高, 释放行为均符合一级动力学方程。随着醚基侧链的微增长, P[C_nOC₂vim]Cl(n=2, 3)凝胶对CIP、Ber累积释放率降低, 释放行为均符合Higuchi动力学方程。该类凝胶在作为肠道抗菌类药物的pH/盐双敏性控释载体方面有一定潜力。