A NOVEL-APPROACH FOR PREPARATION OF PH-SENSITIVE HYDROGELS FOR ENTERIC DRUG DELIVERY
A NOVEL-APPROACH FOR PREPARATION OF PH-SENSITIVE HYDROGELS FOR ENTERIC DRUG DELIVERY
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DOI：
10.1016/0168-3659(91)90072-l
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发表时间：
1991-04-01
影响因子：
10.8
通讯作者：
HOFFMAN, AS
中科院分区：
文献类型：
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作者：
DONG, LC;HOFFMAN, AS
提出了一种制备基于热可逆聚合物的pH敏感性水凝胶的新理论，并据此合成了一类新的水凝胶。 这些特殊的凝胶对温度和pH都敏感，并且比基于聚（甲基丙烯酸羟乙酯-共丙烯酸）或聚（丙烯酰胺-共-丙烯酸）水凝胶的水凝胶对pH变化的响应程度大得多。 在37 ℃时，它们在不带电时高于它们的低临界溶解温度。 因此，在胃pH值（1.4）下，这些凝胶仅含有适量的水，全部为结合水。 但在肠道pH（6.8-7.4）下，它们广泛地膨胀，允许药物如吲哚美辛的持续肠道递送，否则会引起胃刺激。 体外研究表明，在pH 1.4下，24小时内仅释放可忽略量的吲哚美辛，而在pH 7.4下，凝胶中超过90%的总药物在约10分钟内逐渐释放。5小时 在pH 7.4下的释放速率随着凝胶中的非冻结游离水的分数而增加，这与凝胶丙烯酸含量平行。 一个异常的释放曲线，观察到所有的pH敏感的异质性水凝胶在此pH值，这表明溶胀控制机制。
A new rational of preparing pH-sensitive hydrogels based on thermally reversible polymers is proposed, according to which a new class of hydrogels has been synthesized. These special gels are sensitive to both temperature and pH, and respond to the pH change to a much greater extent than hydrogels based on poly(hydroxyethyl methacrylate-coacrylic acid) or poly(acrylamide-co-acrylic acid) hydrogels. At 37-degrees-C, they are above their lower critical solution temperature when uncharged. Therefore, at gastric pH (1.4), these gels contain only a moderate amount of water, all of it as bound water. But at enteric pH (6.8-7.4), they swell extensively, permitting sustained enteric delivery of drugs such as indomethacin, which would otherwise cause stomach irritation. An in vitro study has shown that only a negligible amount of indomethacin is released at pH 1.4 in 24 hours, while at pH 7.4 more than 90% of the total drug in the gels is gradually released over ca. 5 hours. The release rate at pH 7.4 increases with the fraction of non-freezing, free water in the gels, which is in parallel with the gel acrylic acid content. An anomalous release profile was observed for all the pH-sensitive heterogeneous hydrogels at this pH, suggesting a swelling-controlled mechanism.