International Journal of Nanomedicine (Dec 2023)
Rhamnolipid Micelles Assist Azithromycin in Efficiently Disrupting Staphylococcus aureus Biofilms and Impeding Their Re-Formation
Abstract
Shiyu Lin,* Xiaojuan Li,* Yuning Zhang,* Wei Zhang, Gang Shu, Haohuan Li, Funeng Xu, Juchun Lin, Hualin Fu Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hualin Fu, Tel +86 28 82691162, Fax +86 28 82652669, Email [email protected]: Biofilm is highly resistant to antibiotics due to its heterogeneity and is implicated in over 80% of chronic infections; these refractory and relapse-prone infections pose a huge medical burden.Methods: In this study, rhamnolipid (RHL), a biosurfactant with antibiofilm activity, was loaded with the antibiotic azithromycin (AZI) to construct a stable nanomicelle (AZI@RHL) that promotes Staphylococcus aureus (S. aureus) biofilm disruption.Results: AZI@RHL micelles made a destruction in biofilms. The biofilm biomasses were reduced significantly by 48.2% (P< 0.05), and the main components polysaccharides and proteins were reduced by 47.5% and 36.8%, respectively. These decreases were about 3.1 (15.9%), 7.3 (6.5%), and 1.9 (19.5%) times higher compared with those reported for free AZI. The disruption of biofilm structure was observed under a confocal microscope with fluorescent labeling, and 48.2% of the cells in the biofilm were killed. By contrast, the clearance rates of cells were only 20% and 17% when treated alone with blank micelles or free AZI. Biofilm formation was inhibited up to 92% in the AZI@RHL group due to effects on cell auto-aggregation and eDNA release. The rates for the other groups were significantly lower, with only 27.7% for the RHL group and 12% for the AZI group (P< 0.05). The low cell survival and great formation inhibition could reduce biofilm recolonization and re-formation.Conclusion: The antibiofilm efficacy of rhamnolipid was improved through micellar nanoparticle effects when loading azithromycin. AZI@RHL provides a one-step solution that covers biofilm disruption, bacteria inactivation, recolonization avoidance, and biofilm re-formation inhibition. Keywords: Staphylococcus aureus, antibiofilm, rhamnolipid, biosurfactant, nanomicelle
