Complexation hydrogels for intestinal delivery of interferon beta and calcitonin.
Complexation hydrogels for intestinal delivery of interferon beta and calcitonin.
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DOI：
10.1016/j.jconrel.2008.11.014
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发表时间：
2009-03-04
影响因子：
10.8
通讯作者：
Takayama, Kozo
中科院分区：
文献类型：
--
作者：
Kamei, Noriyasu;Morishita, Mariko;Chiba, Hitomi;Kavimandan, Nikhil J.;Peppas, Nicholas A.;Takayama, Kozo
近年来的研究表明，聚甲基丙烯酸-g-乙二醇络合水凝胶（以下简称P(MAA-g-EG)）基于其ph依赖性络合特性、酶抑制作用和黏附特性，具有较高的胰岛素掺入效率和肠内胰岛素快速释放。因此，它们是通过口服途径给药胰岛素的有希望的载体。由于我们将这些水凝胶设计为适合于口服多种多肽/蛋白药物的载体，因此在本研究中我们旨在研究P（MAA-g-EG）水凝胶在改善多种多肽/蛋白药物肠道吸收中的适用性。胰岛素、降钙素和干扰素β在水凝胶中的掺入效率较高。此外，负载降钙素和干扰素β的聚合物微颗粒表现出络合/解络合和ph敏感释放行为。分子量和化学结构似乎根据肽和蛋白质的不同而影响掺入和释放的效率。此外，在封闭的大鼠回肠段注入含有降钙素或干扰素β的颗粒后，观察到血浆钙浓度急剧降低，并伴有钙吸收和血浆干扰素β浓度的剂量依赖性增强。这些发现表明，P（MAA-g-EG）水凝胶是通过口服途径给药各种肽和蛋白质的有希望的载体。
Recent studies have suggested that complexation hydrogels poly(methacrylic acid-g-ethylene glycol) (henceforth designated as P(MAA-g-EG)) exhibit high insulin incorporation efficiency, rapid insulin release in the intestine based on their pH-dependent complexation properties, enzyme-inhibiting effects and mucoadhesive characteristics. Therefore, they are promising carriers for insulin delivery via an oral route. As we designed these hydrogels as carriers suitable for oral administration of various peptide/protein drugs, in this study we aimed at investigating the applicability of P(MAA-g-EG) hydrogels to improving the intestinal absorption of various peptide/protein drugs. High incorporation efficiency into hydrogels was observed for insulin, calcitonin, and interferon β. In addition, polymer microparticles loaded with calcitonin and interferon β exhibited complexation/decomplexation and pH-sensitive release behavior. The molecular weight and chemical structure appeared to affect the efficiency of incorporation and release depending on the peptides and proteins. Furthermore, a drastic reduction of plasma calcium concentration accompanied by calcium absorption and a dose-dependent enhancement of plasma interferon β concentration were observed after the administration of particles loaded with calcitonin or interferon β into closed rat ileal segments. These findings indicate that P(MAA-g-EG) hydrogels are promising carriers for administration of various peptides and proteins via an oral route.
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影响因子：
5.8
作者：
Peppas, NA
通讯作者：
Peppas, NA
影响因子：
3.7
作者：
Takeuchi, H;Yamamoto, H;Kawashima, Y
通讯作者：
Kawashima, Y
影响因子：
3.7
作者：
Aoki, Y;Morishita, M;Takayama, K
通讯作者：
Takayama, K
影响因子：
3.7
作者：
Morishita, M;Aoki, Y;Takayama, K
通讯作者：
Takayama, K
影响因子：
5.8
作者：
MESIHA, M;PLAKOGIANNIS, F;VEJOSOTH, S
通讯作者：
VEJOSOTH, S