NSAIDs bound to methacrylic carriers:: microstructural characterization and in vitro release analysis
NSAIDs bound to methacrylic carriers:: microstructural characterization and in vitro release analysis
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DOI：
10.1016/s0168-3659(01)00212-7
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发表时间：
2001-03-12
影响因子：
10.8
通讯作者：
San Román, J
中科院分区：
文献类型：
--
作者：
Gallardo, A;Parejo, C;San Román, J
基于甲基丙烯酸羟乙酯、HEMA和五种甲基丙烯酸衍生物的共聚物的化学控制的药物递送系统或“聚合物药物”，所述甲基丙烯酸衍生物通过不稳定的酯键MAI、MAK、MAEK、MEI和MEK在其化学结构中引入布洛芬或酮洛芬，已经通过在50 ℃下在溶液中的自由基聚合制备。单体结构中引入了三种不同的间隔基：芳香族酰胺、脂肪族酯和组合的芳香族酰胺/脂肪族酯。甲基丙烯酰胺衍生物与HEMA的共聚反应遵循具有竞聚率值的末端模型，竞聚率值由Tidwell和Mortimer（J. Polym. Sci. A 1965;3：369-378）非线性最小二乘处理，r（MAI）=0.38，r（HEMA）=1.69; r（MAK）=0.30，r（HEMA）=0.48;和r（MAEK）=0.66，r（HEMA）=2.85。根据这些值并考虑到甲基丙烯酸酯MEI和MEK在结构上与HEMA相关，微观结构分析为我们提供了单体单元的随机分布。用于体外实验的富含HEMA的共聚物显示出具有由HEMA单元分离的活性残基的非常高的序列群体。在pH 7.4和9下进行体外释放实验，对于每种共聚物体系使用六种不同的组合物（1、2.5、5、10、20和30重量%的活性丙烯酸单体）。结果显示，根据间隔物的类型，以周为单位的控释具有非常不同的曲线（芳香族酯比脂肪族酯更容易水解），药物（酮洛芬的释放速率高于布洛芬），共聚物的组成具有一般规律，释放速率随着所连接的药物的含量而增加，直到某些组合物由于疏水性和pH的整体增加而使这种作用逆转（在pH 9的强碱性介质中释放速率明显更高）。(C)2001 Elsevier Science B. V.保留所有权利。
Chemically controlled drug delivery systems or 'polymeric drugs' based on copolymers of a-hydroxyethyl methacrylate, HEMA, and five methacrylic derivatives which incorporate ibuprofen or ketoprofen in their chemical structure by means of labile ester bonds, MAI, MAK, MAEK, MEI and MEK, have been prepared by free radical polymerization in solution at 50 degreesC. Three different spacers have been incorporated to the monomer structure: an aromatic amide, an aliphatic ester and a combined aromatic amide/aliphatic ester. Copolymerization reactions of the methacrylamide derivatives with HEMA follow the terminal model with reactivity ratio values, determined by the Tidwell and Mortimer (J. Polym. Sci. A 1965;3:369-378) non-linear least-squares treatment, of r(MAI)=0.38, r(HEMA)=1.69; r(MAK)=0.30, r(HEMA)=0.48; and r(MAEK)=0.66, r(HEMA)=2.85. From these values and considering that the methacrylates MEI and MEK are structurally related to HEMA, the microstructural analysis give us a random distribution of the monomeric units. The HEMA-rich copolymers, used for the in vitro experiments, showed a very high population of sequences with the active residue isolated by HEMA units. The in vitro release experiments were carried out at pH 7.4 and 9, using six different compositions for each copolymer system (1, 2.5, 5, 10, 20 and 30 wt% of the active acrylic monomer). The results show a controlled release in terms of weeks with very different profiles which depend on the type of spacer (the aromatic ester is more susceptible to hydrolysis than the aliphatic one), drug (ketoprofen release rate is higher than the ibuprofen one), composition of the copolymer las a general rule, the release rate increases with the content of the attached drug until some composition where this effect is reverted because of the global increase in hydrophobicity) and pH (the release rate is noticeably higher in a strong basic medium, pH 9). (C) 2001 Elsevier Science B.V. All rights reserved.