Dependence of copolymer composition, swelling history, and drug concentration on the loading of diltiazem hydrochloride (DIL.HCl) into poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels and its release behaviour from hydrogel slabs.
Dependence of copolymer composition, swelling history, and drug concentration on the loading of diltiazem hydrochloride (DIL.HCl) into poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels and its release behaviour from hydrogel slabs.
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DOI：
10.1016/j.jconrel.2004.10.025
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发表时间：
2005-02
期刊：
影响因子：
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通讯作者：
R. Sousa;A. Prior-Cabanillas;I. Quijada-Garrido;J. M. Barrales-rienda
中科院分区：
文献类型：
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作者：
R. Sousa;A. Prior-Cabanillas;I. Quijada-Garrido;J. M. Barrales-rienda
研究了抗高血压阳离子药物盐酸地尔硫卓(DIL.HCl)在聚(N-异丙基丙烯酰胺)[P(N-iPAAm)]、聚(甲基丙烯酸)[P(MAA)]及其聚[(N-异丙基丙烯酰胺)-co-(甲基丙烯酸)]P[(N-iPAAm)-co-(MAA)]水凝胶中的负载及其释放行为。为此，我们测试了两种系列的水凝胶，一种是预先在酸性 pH 下浸泡的（处理过的水凝胶），另一种是合成后用去离子水洗涤的（未处理的水凝胶）。为了载药，这两个系列的水凝胶被浸泡在不同浓度的药物溶液中。分析了凝胶负载的 DIL.HCl 量以及作为水凝胶组成和负载溶液中 DL.HCl 浓度函数的溶胀度。由于 DIL.HCl 和 MAA 基团之间的相互作用，“未经处理”的富集 MAA 共聚物水凝胶呈现出最高的载药量和装载效率。 320 μm/mL 的 DIL.HCl 浓度已用于负载共聚物以进行释放实验，因为在该浓度下，水凝胶可以达到相对较高的载药量，同时仍具有较高的负载效率。在三种介质中测试了释放情况，即淡水（Milli-Q 级，pH 7.0）、0.1 N 氯化氢（pH 1.2）和磷酸盐缓冲液（pH 7.0）。一般来说，淡水和酸性介质中的释放量低于磷酸盐缓冲液中的释放量。为了解释这些结果，考虑了温度、介质和成分对水凝胶 pH 值和热敏感性的影响以及地尔硫卓-聚合物相互作用。
The loading of an antihypertensive cationic drug, diltiazem hydrochloride (DIL.HCl), into poly(N-isopropylacrylamide) [P(N-iPAAm)], poly(methacrylic acid) [P(MAA)], and their poly[(N-isopropylacrylamide)-co-(methacrylic acid)] P[(N-iPAAm)-co-(MAA)] hydrogels as well as their release behaviour have been investigated. For this purpose, two series of hydrogels have been tested, one previously soaked under acidic pH (treated hydrogels) and the other from the synthesis and washed in deionized water (untreated hydrogels). For the drug loading, these two series of hydrogels have been soaked in drug solutions with different concentrations. DIL.HCl amounts loaded by the gels as well as swelling degrees as a function of both hydrogel composition and DL.HCl concentration in the loading solution have been analyzed. Due to the interactions among DIL.HCl and the MAA group, “untreated” enriched MAA copolymer hydrogels present the highest drug load and loading efficiency. A DIL.HCl concentration of 320 μm/mL has been employed to load copolymers for release experiments, because for this concentration, hydrogels reach relative high drug load with a still high efficiency of loading. Release has been tested in three media, namely, fresh water (Milli-Q grade, pH 7.0), 0.1 N hydrogen chloride (pH 1.2), and a phosphate buffer (pH 7.0). In general, release is lower in fresh water and acidic media than in phosphate buffer. To explain these results, the effect of temperature, medium, and composition on the pH and thermo sensitivity of the hydrogels as well as the diltiazem–polymer interactions have been taken into account.