Copolymers synthesized from acrylic acid and methacrylic acid used as gastroprotective and mucoadhesive enteric coatings have been used to prepare micro- (∼2 μm), submicro- (∼200 nm), and nanoparticles (∼20 nm) containing rifampicin (Rif) to obtain time-controlled drug release kinetics. Different particle sizes and drug release kinetics have been obtained using different synthesis conditions and fabrication techniques including the use of an electrosprayer and an interdigital microfabricated micromixer. The antimicrobial action of the encapsulated Rif has been demonstrated against Staphylococcus aureus ATCC 25923 and compared with the effect of the equivalent dose of the free macrolide antibiotic. At low concentrations, the encapsulated antibiotic showed superior antimicrobial activity than the free drug. The stability of the developed particles has been evaluated in vitro under simulated gastric and intestinal conditions. At the concentrations tested, a reduced cytotoxicity against different human cell lines was observed after analyzing their subcytotoxic doses and the influence on their cell cycle by flow cytometry. Drug release kinetics can be tuned by adjusting particle sizes, and it would be possible to reach the minimum inhibitory concentration or the minimum bactericidal concentration at different time points depending on the medical needs.

中文翻译：

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使用独立于pH值的粘膜粘附性聚合物控制口服抗生素持续递送中的粒径和释放动力学。

由丙烯酸和甲基丙烯酸合成的用作胃保护和粘膜粘附性肠溶衣的共聚物已用于制备微米（〜2μm），亚微米（〜200 nm）和含有利福平（Rif）的纳米颗粒（〜20 nm），从而获得时间控制的药物释放动力学。使用不同的合成条件和制造技术（包括使用电喷雾器和叉指式微制造的微混合器）已经获得了不同的粒径和药物释放动力学。已证明包封的Rif的抗微生物作用对金黄色葡萄球菌并与ATCC 25923等效剂量的游离大环内酯类抗生素比较。在低浓度下，包封的抗生素显示出比游离药物优越的抗菌活性。已经在模拟的胃和肠条件下在体外评估了所形成的颗粒的稳定性。在测试的浓度下，通过流式细胞仪分析其亚细胞毒性剂量及其对细胞周期的影响后，观察到针对不同人类细胞系的细胞毒性降低。药物释放动力学可以通过调节粒径来调节，并且有可能根据医疗需求在不同时间点达到最小抑菌浓度或最小杀菌浓度。