School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, No. 16866 East Road of Jingshi, Jinan 250200, Shandong Province, PR China; Shandong Academy of Medical Sciences, No. 18877 Jingshi Road, Jinan 250062, Shandong Province, PR China.
School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China.
J Colloid Interface Sci. 2017 Jun 15;496:16-25. doi: 10.1016/j.jcis.2017.02.011. Epub 2017 Feb 9.
In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment.
为了提高阿奇霉素在酸性介质中的抗菌活性，以甲氧基聚乙二醇（mPEG）为原料，通过烯丙基化、自由基加成、开环聚合和酰胺化反应合成了单甲氧基聚（乙二醇）-嵌段-聚（天冬氨酸-接枝-咪唑）共聚物。薄膜水化法制备的载阿奇霉素胶束的载药量和包封率分别为 11.58±0.86%和 96.06±1.93%。载药胶束在 pH5.5-7.8 范围内表现出粒径和zeta 电位的 pH 依赖性。它可以控制药物的体外释放，并在 pH6.0 时表现出比 pH7.4 时更高的释放速率。体外抗菌实验表明，载药胶束对金黄色葡萄球菌的活性在 pH6.0 和 pH7.4 的介质中均优于游离阿奇霉素。用荧光素作为具有 pH 依赖性荧光强度降低特性的替代物，激光共聚焦荧光显微镜分析证实，由于共聚物咪唑基团在 pH6.0 时质子化，胶束的细胞摄取得到了提高。与游离药物相比，药物在酸性介质中的摄取增加和释放增加导致其活性增强。胶束药物递送系统在细菌感染治疗领域具有潜在的应用前景。
