Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections

Background: Biofilm-associated lung infections, particularly those caused by Staphylococcus aureus (S. aureus), pose significant clinical challenges to conventional therapies. S. aureus Biofilm infections are refractory to treatment due to the presence of persister bacterial cells and the barrier effect of unique extracellular polymeric substances (EPS). Results: This study describes the development of multifunctional micelles, HK-SL Ms, utilizing sophorolipid (SL) to encapsulate Honokiol (HK). HK-SL Ms potently disrupted the EPS barrier, killed some internal colonizing bacteria, and inhibited further bacterial adhesion. Consequently, the dynamic cycling of biofilms was hindered, achieving a promising removal of S. aureus biofilms. In vitro studies demonstrated that HK-SL Ms exhibited significant antimicrobial reduction of a 6.42 log₁₀CFU/mL. HK-SL Ms eradicated 71.73% of biofilms by targeting extracellular polysaccharides, extracellular proteins, and viable cells within the biofilm. Additionally, 1.66 log₁₀CFU/mL units of S. aureus within biofilms were killed. Moreover, HK-SL Ms inhibited 91.10% of early S. aureus biofilm formation by obstructing initial bacterial adhesion and the formation of extracellular polysaccharides and polysaccharide intercellular adhesins (PIA). Thus, the reestablishment and reinfection of S. aureus biofilms could be resolved promisingly. Biofilm infections are as predominant in acute pneumonia as in chronic cases, inducing similar lung inflammation. In a murine model of pneumonia infected by S. aureus, HK-SL Ms significantly reduced the bacterial load in the lungs, decreased inflammatory factor levels, and repaired lung tissue damage. Conclusions: HK-SL Ms offers a novel strategy for the clinical treatment of biofilm-associated infections by dispersing and removing S. aureus biofilms and preventing new infections.