Davaran S, Hanaee J, Khosravi A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabriz, Tabriz, Iran.
J Control Release. 1999 Apr 19;58(3):279-87. doi: 10.1016/s0168-3659(98)00167-9.
New acrylic type polymeric systems having degradable ester or amide bonds linked to the bioactive agent 5-amino salicylic acid (5-ASA), were prepared and evaluated as materials for colon-specific drug delivery. Methacryloyloxyethyl 5-amino salicylate (MOES), and N-methacryloylaminoethyl 5-amino salicylamide (MAES) were prepared as the polymerizable derivatives of 5-ASA using activated ester methodology. The drug-containing monomers were free radically copolymerized with methacrylic acid or hydroxyethyl methacrylate, utilizing azobisisobutyronitrile as initiator. The polymer bearing 5-ASA units as side substituents of the acrylic backbone were obtained in the form of poly pendent esters or poly pendent amides. The drug release studies were performed by hydrolysis in buffered solutions (pH 1, 7.2, 8.5), or simulated intestinal fluid containing pancreatin to measure the chemical degradation expected to occur in the intestinal tract. The release profiles indicated that the hydrolytic behavior of polymers strongly depends on their degree of swelling, type of comonomer, and the nature of hydrolyzable bond. Implication of the results for use of these polymers for colon targeting are discussed.
制备了新型丙烯酸类聚合物体系，其具有与生物活性剂5-氨基水杨酸（5-ASA）相连的可降解酯键或酰胺键，并将其作为结肠特异性药物递送材料进行了评估。采用活性酯法制备了5-氨基水杨酸甲酯丙烯酸酯（MOES）和N-甲基丙烯酰基氨基乙基5-氨基水杨酰胺（MAES）作为5-ASA的可聚合衍生物。以偶氮二异丁腈为引发剂，将含药单体与甲基丙烯酸或甲基丙烯酸羟乙酯进行自由基共聚。得到了以丙烯酸主链的侧基取代基形式存在的含5-ASA单元的聚合物，即聚侧酯或聚侧酰胺。通过在缓冲溶液（pH 1、7.2、8.5）中水解或在含有胰酶的模拟肠液中进行药物释放研究，以测量预期在肠道中发生的化学降解。释放曲线表明，聚合物的水解行为强烈取决于其溶胀程度、共聚单体类型和可水解键的性质。讨论了这些聚合物用于结肠靶向的结果的意义。
