Background: This study aimed to reduce the amount of sulfobutylether-β-cyclodextrin (SBECD) used in
the marketed voriconazole injections to meet the clinical needs of patients with moderate-to-severe renal impairment
(creatinine clearance rate <50 mL/min).
Objective: This study found that the surfactant Kolliphor® HS 15 (HS 15) and SBECD had significant synergistic
effects on solubilizing voriconazole, and a novel voriconazole complex delivery system (VRC-CD/HS 15) was
Methods: The complex system was characterized, and its antifungal activity was studied by dynamic light scattering,
dialysis bag method, disk diffusion, and broth microdilution.
Results: Compared with the control, its encapsulation efficiency (90.07±0.48%), drug loading (7.37±0.25%) and zeta
potential (-4.36±1.37 mV) were increased by 1.54%, 41.19%, and 296.36%, respectively; its average particle size
(13.92±0.00 nm) was reduced by 15.69%, so the complex system had better stability. Simultaneously, its drug release
behavior was similar to that of the control, and it was a first-order kinetic model. Antifungal studies indicated that the
complex system had noticeable antifungal effects. With the increase of drug concentration, the inhibition zone
increased. The minimum inhibitory concentrations of the complex system against Cryptococcus neoformans,
Aspergillus niger and Candida albicans were 0.0313 μg/mL, 1 μg/mL and 128 μg/mL, respectively.
Conclusion: It showed a significant inhibitory effect on C. neoformans and had a visible therapeutic effect on
Kunming mice infected with C. neoformans. Consequently, VRC-CD/HS 15 had better physicochemical properties
and still had an apparent antifungal effect, and was promising as a potential alternative drug for clinical application.