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Azithromycin-loaded linolenic acid-modified methoxy poly(ethylene glycol) micelles for bacterial infection treatment

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Abstract

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.

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Funding

This work is supported by Natural Science Foundation of Shandong Province under Grant number ZR2016BL15 and Science and Technology Project of University of Jinan under Grant number XKY1732.

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Authors and Affiliations

  1. School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan, 250022, Shandong Province, People’s Republic of China

    Yi Wen, Zhimei Song, Hongmei Xu, Li Zhu & Runliang Feng

  2. School of Basic Medical Sciences, Dali University, Dali, 671000, Yunnan, People’s Republic of China

    Sijia Feng

  3. The People’s Hospital of Guangrao, Guangrao, 257300, Shandong Province, People’s Republic of China

    Fangfang Teng

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  1. Yi Wen
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Correspondence to Runliang Feng.

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Wen, Y., Song, Z., Xu, H. et al. Azithromycin-loaded linolenic acid-modified methoxy poly(ethylene glycol) micelles for bacterial infection treatment. Drug Deliv. and Transl. Res. 12, 550–561 (2022). https://doi.org/10.1007/s13346-021-00953-2

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