Biocompatibility and drug release behavior of spontaneously formed phospholipid polymer hydrogels.
Biocompatibility and drug release behavior of spontaneously formed phospholipid polymer hydrogels.
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DOI：
10.1002/jbm.a.30864
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
M. Kimura;M. Takai;K. Ishihara
中科院分区：
文献类型：
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作者：
M. Kimura;M. Takai;K. Ishihara
含有2-甲基丙烯酰氧乙基磷酰胆碱（MPC）部分的水凝胶形成从水溶液与水溶性MPC聚合物与羧酸和烷基基团，因为氢键的形成。为了研究水凝胶的生物相容性和药物释放行为，我们使用了无规和嵌段型羧酸MPC聚合物，例如聚[MPC-co-甲基丙烯酸（MA）]（rPMA）、聚[MPC-co-4-甲基丙烯酸（MA）]（rPMA）和聚[MPC-co-4-甲基丙烯酸（MA）]（rPMA）。（2-甲基丙烯酰氧基乙基）偏苯三酸（MET）]（rPMT），聚在一些实施方案中，MPC聚合物包括聚（MA-嵌段-MPC-嵌段-MA）（bPMA）和聚（MET-嵌段-MPC-嵌段-MET）（bPMT），以及烷基MPC聚合物，例如聚[MPC-共-甲基丙烯酸正丁酯]（PMB）和聚（MPC-共-甲基丙烯酸苄酯）（PMBz）。我们通过溶血试验和体内注射试验研究了自发形成的MPC聚合物水凝胶的生物相容性。与嵌段聚合物相比，具有羧酸基团的无规MPC聚合物表现出更强的溶血活性。体内注射试验的结果还表明羧酸聚合物的生物相容性低，特别是在高浓度下。在溶血试验和体内注射试验中，烷基MPC聚合物、PMB和PMBz显示出优异的生物相容性。然而，水凝胶，rPMA/PMB水凝胶（rABgel）和rPMT/PMBz水凝胶（rTZgel）降低了元素聚合物，rPMA和rPMT的溶血活性。因此，抑制羧酸基团的离子化对于生物相容性是必要的。我们还研究了药物的释放行为，注意到聚合物和药物之间的相互作用。相对低分子量的亲水性药物5-氟尿嘧啶的释放行为不依赖于聚合物的结构。较高分子量的药物，酮洛芬和吲哚美辛，从嵌段聚合物水凝胶比随机聚合物水凝胶，rAB凝胶释放更快，而最高分子量的药物，阿霉素，从随机聚合物水凝胶释放更快。一个可能的原因是分子结构的差异;也就是说，在嵌段聚合物中分离的亲水和疏水部分构建了药物可以扩散的路径。此外，rTZgel抑制了具有大量芳环的药物的释放，这可能是由于堆叠效应。压缩试验结果也表明rTZgel和药物之间存在堆积效应。基于这些结果，可以通过选择具有适当化学结构的储库与药物相互作用来控制药物释放。例如，具有较少芳环的相对线性结构的药物的释放可以在rAB凝胶中而不是在rTZgel中被抑制。因此，可以得出结论，如果电离受到抑制，这些MPC聚合物水凝胶可以用作药物储存器的材料，可以根据药物进行选择。
Hydrogels containing 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties were formed from aqueous solutions with water-soluble MPC polymers with carboxylic acid and alkyl groups because of hydrogen bonding formation. To investigate the biocompatibility and drug release behavior of the hydrogels, we used random- and block-type carboxylic acid MPC polymers, such as poly [MPC-co-methacrylic acid (MA)] (rPMA), poly[MPC-co-4-(2-methacryloyloxyethyl) trimellitic acid (MET)] (rPMT), poly (MA-block-MPC-block-MA) (bPMA) and poly(MET-block-MPC-block-MET) (bPMT), and alkyl MPC polymers, such as poly[MPC-co-n-butyl methacrylate] (PMB) and poly(MPC-co-benzyl methacrylate) (PMBz). We investigated the biocompatibility of the spontaneously formed MPC polymer hydrogels by a hemolysis test and an in vivo injection test. The random MPC polymers having carboxylic acid groups expressed more hemolytic activity compared to the block polymers. The results of the in vivo injection test also indicated low biocompatibility of the carboxylic acid polymers especially at high concentration. The alkyl MPC polymers, the PMB and PMBz showed excellent biocompatibility in both hemolysis and in vivo injection test. However, the hydrogels, the rPMA/PMB hydrogel (rABgel) and the rPMT/PMBz hydrogel (rTZgel) lowered the hemolytic activity of elemental polymers, the rPMA and rPMT. Thus, suppression of the ionization of the carboxylic acid groups is necessary for biocompatibility. We also investigated the drug release behavior with attention to the interaction between the polymer and the drugs. The release behavior of a relatively low-molecular-weight hydrophilic drug, 5-fluorouracil, did not depend on the structure of the polymers. The higher-molecular-weight drugs, ketoprofen and indomethacin, were released faster from the block polymer hydrogel than the random polymer hydrogel, the rABgel, while the highest-molecular-weight drug, doxorubicin, was released faster from the random polymer hydrogel. A probable reason for this is the difference in the molecular structure; that is, the separated hydrophilic and hydrophobic sections in the block polymers constructed pathways where a drug can diffuse. In addition, the rTZgel suppressed the release of a drug with a large number of aromatic rings probably because of the stacking effect. The results of the compression test also suggested the existence of the stacking effect between the rTZgel and the drugs. Based on these results, control of drug release is possible by selecting a reservoir with an appropriate chemical structure to interact with the drug. For example, release of a relatively linear-structured drug with less aromatic rings can be suppressed in the rABgel rather than in the rTZgel. Thus, it can be concluded that if the ionization is suppressed, these MPC polymer hydrogels can be used as a material for a drug reservoir that can be selected according to the drug.