New amphiphilic and pH-sensitive hydrogel for controlled release of a model poorly water-soluble drug
New amphiphilic and pH-sensitive hydrogel for controlled release of a model poorly water-soluble drug
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DOI：
10.1016/j.ejpb.2009.07.008
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发表时间：
2009-11-01
影响因子：
4.9
通讯作者：
Le Cerf, D.
中科院分区：
文献类型：
--
作者：
Colinet, I.;Dulong, V.;Le Cerf, D.
本文介绍了基于海藻酸盐-g-PCL的新型pH敏感、两亲性和生物相容性水凝胶的开发，该水凝胶与钙离子交联形成微球，用于控制难溶药物的释放。我们重点研究了PCL链的长度(530和1250gmol(-1))的影响。溶胀曲线清楚地表明，这些水凝胶在模拟胃液(pH 1.2)中轻微膨胀(10-14%)，在模拟肠液(pH 6.8)中强烈膨胀(崩解前为700-1300%)。在两种介质中，由于疏水性的PCL接枝，基于两亲性衍生物的微球的溶胀率都低于海藻酸盐/钙离子微球，并且随着疏水性的增加而降低。模型药物茶碱被包裹在这些水凝胶中，并进行了释放研究。药物在酸性流体中受到保护(海藻酸盐-g-PCL水凝胶在350分钟内仅释放14-20%，而海藻酸盐水凝胶释放35%)。由于离子交换和水凝胶的解体，药物在中性液体中完全释放。PCL导致海藻酸盐-g-PCL/Ca~(2+)微球在SIF中的释药动力学降低(海藻酸盐-g-PCL/Ca~(2+)微球为2 h，海藻酸盐/Ca~(2+)微球为1 h)。研究表明，在盐介质中，通过530gmol(-1)的PCL接枝物之间的分子内相互作用在微球内建立团簇，可以保留药物并显著减缓其释放。(C)2009爱思唯尔B.V.保留所有权利。
This paper presents the development of new pH-sensitive, amphiphilic and biocompatible hydrogels based on alginate-g-PCL, cross-linked with calcium ions to form beads, prepared for controlled delivery of poorly water-soluble drug. We have focused Our study on the effect of the length of PCL chains (530 and 1250 g mol(-1)). Swelling profiles obtained clearly indicated that these hydrogels swell slightly (10-14%) in a simulated gastric fluid (pH 1.2), and strongly (700-1300% before disintegration) in a simulated intestinal fluid (pH 6.8). In both media, rates of swelling were lower for beads based on amphiphilic derivatives than for alginate/Ca2+ ones due to the hydrophobic PCL grafts, and decreased when hydrophobic character increased. A model drug, theophylline, was entrapped into these hydrogels and release studies were carried out. The drug was protected in acidic fluid (only 14-20% of release for alginate-g-PCL hydrogel against 35% of release for alginate hydrogel during 350 min). The drug is released completely in neutral fluid due to ion exchanges and disintegration of the hydrogel. PCL leads to decrease in the release kinetics in SIF (2 h for alginate-g-PCL/Ca2+ beads against 1 h for alginate/Ca2+ beads). It was demonstrated that the establishment of clusters inside beads by intramolecular interactions between PCL grafts of 530 g mol(-1) in salt media allowed to retain the drug and to slow down its release considerably. (C) 2009 Elsevier B.V. All rights reserved.