Department of Materials Science and Engineering, Faculty of Materials Science and Chemical Engineering , Ningbo University , Ningbo 315211 , China.
State Key Laboratory of Silicon Materials , Zhejiang University , Hangzhou 310027 , China.
ACS Appl Mater Interfaces. 2018 Nov 7;10(44):38449-38458. doi: 10.1021/acsami.8b14016. Epub 2018 Oct 25.
We present the design of a novel pH-responsive drug release system that is achieved by solventless encapsulation of drugs within a microporous membrane using a thin capping layer of biodegradable poly(methacrylic anhydride) (PMAH) coating. The coating was synthesized via a mild vapor polymerization process, namely, initiated chemical vapor deposition, which allowed perfect retention of the anhydride groups during deposition. The synthesized polyanhydride underwent degradation upon exposure to aqueous buffers, resulting in soluble poly(methacrylic acid). The degradation behavior of PMAH is highly pH-dependent, and the degradation rate under pH 10 is 15 times faster than that under pH 1. The release profile of a model drug rifampicin clearly exhibited two stages: the initial stage when the coatings were being degraded but the drugs were well stored and the second stage when drugs were gradually exposed to the medium and released. The drug release also showed strong pH responsiveness where the duration of the initial stage under pH 1 was more than 7 and 3 times longer than that under pH 10 and 7.4, respectively, and the release rates at pH 7.4 and 10 were significantly faster than that at pH 1. The pH-dependent degradation of the encapsulant thus enabled good preservation of drugs under low-pH environment but high drug release efficiency under neutral and alkaline environment, suggesting potential applications in site-specific drug delivery systems.
我们提出了一种新颖的 pH 响应药物释放系统的设计，该系统通过使用生物可降解的聚（甲基丙烯酰酐）（PMAH）薄封盖层在微孔膜内无溶剂包封药物来实现。该涂层通过温和的气相聚合过程，即引发化学气相沉积合成，在沉积过程中完美保留了酸酐基团。合成的聚酸酐在暴露于水性缓冲液时会降解，生成可溶的聚（甲基丙烯酸）。PMAH 的降解行为高度依赖 pH 值，在 pH 值为 10 下的降解速度比在 pH 值为 1 下快 15 倍。模型药物利福平的释放曲线明显显示出两个阶段：第一阶段是涂层正在降解但药物被良好储存的阶段，第二阶段是药物逐渐暴露于介质并释放的阶段。药物释放也表现出很强的 pH 响应性，在 pH 值为 1 下的初始阶段持续时间超过 7 倍，比在 pH 值为 10 和 7.4 下分别长 3 倍，在 pH 值为 7.4 和 10 下的释放速度明显快于在 pH 值为 1 下的释放速度。因此，封装剂的 pH 依赖性降解可以在低 pH 值环境下很好地保存药物，但在中性和碱性环境下具有较高的药物释放效率，这表明其在靶向药物传递系统中有潜在的应用。
