School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan, 250022, Shandong Province, People's Republic of China.
School of Basic Medical Sciences, Dali University, Dali, 671000, Yunnan, People's Republic of China.
Drug Deliv Transl Res. 2022 Mar;12(3):550-561. doi: 10.1007/s13346-021-00953-2. Epub 2021 Mar 14.
In the study, new polymeric micelles loaded with azithromycin were prepared to enhance azithromycin's solubility and evaluate its in vitro/in vivo antibacterial activity against Staphylococcus aureus. Amphiphilic α-Linolenic acid-methoxy poly (ethylene glycol) polymer (MPEG-LNA) was synthesized through DCC-DMAP esterification procedure. Through thin-film hydration method, optimized azithromycin-loaded micelles (AZI-M) were prepared with 87.15% of encapsulation efficiency and 11.07% of drug loading capacity when the ratio of LNA to MPEG was 4. Azithromycin's water-solubility was obviously enhanced due to its loading into the polymeric micelles. The azithromycin-loaded micelles were characterized in terms of x-ray diffraction, Fourier transform infrared spectroscopy, in vitro release, and in vitro/in vivo antibacterial experiments. Although the drug-loaded micelles provided a slow and continuous azithromycin's release in comparison with free azithromycin, in vitro antibacterial activity results confirmed that its effect on the inhibition of bacterial growth and biofilm formation was similar to free azithromycin. It is more interesting that the azithromycin-loaded micelles achieved good in vivo antibacterial therapeutic effect like QiXian® (azithromycin lactobionate injection) in mouse model of intraperitoneal infection. AZI-M can be considered as a potential candidate for in vivo antibiotic therapy of Staphylococcus aureus infections.
在这项研究中，制备了载阿奇霉素的新型聚合胶束以提高阿奇霉素的溶解度，并评价其对金黄色葡萄球菌的体外/体内抗菌活性。通过 DCC-DMAP 酯化程序合成两亲性 α-亚麻酸-甲氧基聚乙二醇聚合物（MPEG-LNA）。通过薄膜水化法，当 LNA 与 MPEG 的比例为 4 时，制备出包封率为 87.15%、载药量为 11.07%的优化阿奇霉素载药胶束（AZI-M）。由于阿奇霉素被载入聚合物胶束中，其水溶性明显提高。对载药胶束进行了 X 射线衍射、傅里叶变换红外光谱、体外释放和体外/体内抗菌实验的表征。虽然与游离阿奇霉素相比，载药胶束提供了缓慢而持续的阿奇霉素释放，但体外抗菌活性结果证实，其抑制细菌生长和生物膜形成的效果与游离阿奇霉素相似。更有趣的是，在金黄色葡萄球菌腹腔感染的小鼠模型中，阿奇霉素载药胶束的体内抗菌治疗效果与齐先®（阿奇霉素乳糖酸盐注射液）相当。AZI-M 可被视为治疗金黄色葡萄球菌感染的体内抗生素治疗的潜在候选药物。
