Abstract
Silibinin-loaded micelle/liposome nanocarriers (SMLNs) were successfully synthesized and characterized using FT-IR, SEM, TEM, XRD and TGA analyses. The nanocarriers exhibited an average particle size of 16.33 nm as determined by TEM imaging and less than 60 nm by FE-SEM analysis. They displayed an amorphous structure, and high thermal stability, maintaining integrity at temperatures exceeding 650 °C. The silibinin loading content and entrapment efficiency were 3.2% and 83.3%, respectively. In vitro release studies demonstrated a rapid, pH-dependent release, achieving complete drug release within 60 min at pH 5.0 and 65 min at pH 7.4. The combination of SMLNs with ciprofloxacin produced strong synergistic antibacterial effects, reducing the minimum inhibitory concentration (MIC) of ciprofloxacin by 2- to 128-fold against resistant E. coli isolates. Biofilm formation decreased significantly under combination therapy compared with ciprofloxacin alone. Quantitative RT-PCR revealed that co-treatment downregulated efflux pump (acrA, acrB and tolC) and virulence (fimH and sfa) genes, while upregulating the repressor gene acrR. Molecular docking confirmed strong binding of silibinin to AcrAB-TolC, acrR, and fimH with binding affinities ranging from - 6.0 to - 8.9 kcal/mol.These findings demonstrate that SMLNs enhance the antibacterial efficacy of ciprofloxacin by inhibiting efflux pumps and biofilm formation, highlighting their potential as a multifunctional nanoplatform to combat antibiotic-resistant E. coli. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04604-y.