In the present study, the association of a new hydrophobic triazole derivative, itraconazole, with intravenously compatible drug carriers (liposomes, cholesterol complexes, nanospheres) was evaluated and the different association yields compared. We tried to elucidate the mechanism of drug-carrier association by means of dilution and zeta potential measurement in the most promising formulations. The different lipid-based drug carriers yielded low association efficiencies (< O h % ) , whereas itraconazole loading into chemically modified p-cyclodextrin nanospheres reached 6.8% (0.170 mg/mL). The longer the hydrophobic chain linked to the p-cyclodextrin, the higher the association of itraconazole within the nanospheres. The highest association yields, 4.1% (0.510 mg/mL), were obtained with nanospheres composed of the most hydrophobic polymer tested, poly-e-caprolactone, and a negatively charged steroidal surfactant, sodium deoxycholate. ltraconazole seems to be both included in the matrix (40%) and adsorbed at the surface of the nanospheres (60%). This may explain the nanosphere instability with time because of continuous itraconazole desorption from the nanospheres, although the nanosphere mean size remained unchanged. The enhanced association yields observed with sodium deoxycholate were not the result of electrostatic attraction between itraconazole (a weak base) and the negatively charged surfactant but rather to stronger hydrophobic interactions between itraconazole and sodium deoxycholate, and to increased specific area of sodium deoxycholate-coated nanospheres. This latter was due to the smaller mean diameter (80 nm) of the sodium deoxycholate-coated nanospheres compared with non ionic surfactant-coated nanospheres (130 nm). o 19% Wiley-Liss, Inc.