Chemistry Department, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
Drug Deliv. 2010 Apr;17(3):158-63. doi: 10.3109/10717541003604908.
The purpose of this study is to develop novel intestinal specific drug delivery systems with pH-sensitive swelling and drug release properties. Acryloyl ester of 5-[4-(hydroxy phenyl) azo] salicylic acid (HPAS) as an azo derivative of 5-amino salicylic acid (5-ASA) was prepared under mild conditions. The HPAS was covalently linked with acryloyl chloride, abbreviated as APAS. Cubane-1,4-dicarboxylic acid (CDA), linked to two 2-hydroxyethyl methacrylate (HEMA) groups, was the cross-linking agent (CA). Methacrylic-type polymeric prodrugs were synthesized by free radical copolymerization of methacrylic acid, poly(ethyleneglycol monomethyl ether methacrylate), and APAS in the presence of cubane cross-linking agent. The effect of copolymer composition on the swelling behavior and hydrolytic degradation were studied in simulated gastric (SGF, pH 1) and intestinal fluids (SIF, pH 7.4). The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 1 and pH 7.4) at 37 degrees C. Detection of the hydrolysis product by UV spectroscopy shows that the azo prodrug (HPAS) was released by hydrolysis of the ester bond located between the HPAS and the polymer chain. Drug release studies showed that the increasing content of MAA in the copolymer enhances hydrolysis in SIF. These results suggest that pH-sensitive systems could be useful for preparation of a muccoadhesive system and controlled release of HPAS as an azo derivative of 5-amino salicylic acid (5-ASA).
本研究旨在开发具有 pH 敏感性溶胀和药物释放性能的新型肠道特异性药物传递系统。在温和条件下，通过将 5-[4-(羟基苯基)偶氮]水杨酸（HPAS）作为 5-氨基水杨酸（5-ASA）的偶氮衍生物与丙烯酰氯反应，制备了 HPAS。HPAS 与丙烯酰氯共价连接，缩写为 APAS。通过自由基共聚将联苯-1,4-二羧酸（CDA）与两个 2-羟乙基甲基丙烯酸酯（HEMA）基团连接起来，作为交联剂（CA）。通过在立方烷交联剂存在下，将甲基丙烯酸、聚乙二醇单甲醚甲基丙烯酸酯和 APAS 进行自由基共聚，合成了甲基丙烯酸型聚合前药。研究了共聚物组成对模拟胃（SGF，pH 1）和肠道液（SIF，pH 7.4）中的溶胀行为和水解降解的影响。通过傅里叶变换红外光谱（FTIR）确定了交联三维聚合物的组成。在含有水缓冲溶液（pH 1 和 pH 7.4）的纤维素膜透析袋中进行药物-聚合物缀合物的水解，在 37°C 下进行。通过紫外光谱法检测水解产物表明，通过位于 HPAS 和聚合物链之间的酯键的水解，释放出偶氮前药（HPAS）。药物释放研究表明，共聚物中 MAA 的含量增加会增强在 SIF 中的水解。这些结果表明，pH 敏感体系可用于制备粘膜粘附系统和 HPAS（5-ASA 的偶氮衍生物）的控释。
