Our previous work has shown that dioctadecyldimethylammonium bromide (DODAB) bilayer fragments (BF) presented antimicrobial activity, solubilized fungicides, e.g., amphotericin B and miconazole (MCZ), stabilized hydrophobic drug particles and were effective in vivo. Here, the interaction between MCZ and DODAB BF is evaluated from determination of BF loading capacity and effects of drug-to-lipid molar proportion (MP) on particle size, zeta potential and gel-to-liquid-crystalline phase transition Tm. DODAB BF solubilized MCZ over a range of MP. BF loading capacity was 0.5 mM MCZ at 5 mM DODAB. Above this limit, the drug aggregated in the dispersion. At pH 6.3, BF zeta potentials decreased with MP, suggesting insertion of deprotonated drug into the bilayer. MCZ optical spectra in BF were similar to those in best organic solvent, confirming drug solubilization. At MP ≤1:10, BF Tm remained unchanged, suggesting drug capture at BF hydrophobic edges. At MP ≥1:10, Tm decreased, showing MCZ insertion into DODAB bilayer. However, drug was expelled from the bilayer core upon lowering temperature. Minimal fungicidal concentrations against C. albicans were synergically reduced by 10 times for drug/BF. © 2005 Elsevier Inc. All rights reserved.