Micelles-Encapsulated with Azithromycin and Ibuprofen for Synergistic Antibacterial at Different pH

• Published in: Journal of pharmaceutical innovation 2024-08, Vol.19 (4), Article 44
• Main Authors: Feng, Runliang, Chen, Shiyu, Zhao, Yingshun, Wang, Mingzhu, Li, Yuli, Jia, Yunjing, Song, Zhimei
• Format: Article
• Language: English
• Subjects: Biochemical Engineering; Biomedical and Life Sciences; Biomedicine; Biotechnology; Industrial and Production Engineering; Original Article; Pharmacology/Toxicology
• ISSN: 1872-5120; 1939-8042
• DOI: 10.1007/s12247-024-09853-7

Purpose To improve azithromycin’s antibacterial activity at different pH through combination therapy. Method Azithromycin- and ibuprofen-loaded micelles were fabricated by the self-assembly of MPEG-PVL copolymer, respectively. Results The drug-loaded micelles had controlled drug release property with water-solubility improvement. Notably, at pH 7.4 or 6.0, the in vitro antibacterial experiments demonstrated that there was no synergistic effect for the two native drugs against S. aureus , but a significant synergy was observed when the two preparations were used in combination. In vitro PI fluorescence staining experiment demonstrated that the introduction of ibuprofen-loaded micelles obviously increased cellular uptake under low concentration of azithromycin-loaded micelles. Through SEM and spectral evaluation experiments, it was found that ibuprofen-loaded micelles could increase the cell permeability by interacting with proteins and phospholipids in the cell membrane, which was conducive to promoting azithromycin-loaded micelles to enter the cells and play a drug effect. Conclusion The azithromycin- and ibuprofen-loaded micelles with synergistically enhanced antibacterial activity are potential candidates for effective bacterial combination therapy. Graphical Abstract