Kolliphor® HS 15-cyclodextrin Complex for the Delivery of Voriconazole: Preparation, Characterization, and Antifungal Activity

Abstract

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 moderateto-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 established. Method: The complex system was characterized, and its antifungal activity was studied by dynamic light scattering, dialysis bag method, disk diffusion, and broth microdilution. Result: 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 concentration 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.