Ocular pharmacokinetics of topical administration of butenafine nanomicelles in rabbit eyes / 中华实验眼科杂志

ABSTRACT

Objective:To study the pharmacokinetics of the broad-spectrum antifungal drug butenafine nanomicelles (BTF-NM) after topical instillation.Methods:The self-assembly method was used to prepare BTF-NM.The particle size, Zeta potential, and polydispersity index (PDI) of BTF-NM were measured by a nano-particle size-Zeta potential analyzer, and the encapsulation efficiency was determined by high-performance liquid chromatography (HPLC). Forty-two healthy New Zealand white rabbits without eye disease were randomly divided into the BTF-NM group and the BTF suspension (BTF-S) group.The corresponding drugs were instilled in the conjunctival sac with a single instillation of 50 μl.The 7.5 mm filter paper was placed in the conjunctival sac of rabbit eye for 1 minute at 5, 15, 30, 60, 120, 180, 240 minutes after the administration.Then the rabbits were sacrificed by intravenous injection of 4% sodium pentobarbital solution through the ears of the rabbits.The aqueous humor was extracted and the corneal tissue was dissected.The drug concentration of BTF in different tissues was measured by HPLC.The study was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HNEECA-2019-01).Results:The particle size and PDI of BTF-NM were (15.65±0.04)nm and 0.11±0.01, respectively, the Zeta potential was (-0.29±0.36)mV, the encapsulation rate was (98.38±0.29)%.The peak time of the drug both in tears and corneal tissues after BTF-NM application was 5 minutes.The peak concentrations of the drug in tears and corneas of the BTF-NM group were (485.21±66.29) μg/g and (12.53±2.32) μg/g, which were 5.6 and 78 times than that of the BTF-S group, respectively.Within the observation time, the mass fractions of the drug in tears and corneas of the BTF-NM group at each time point were significantly higher than those of BTF-S group at corresponding time points (all at P<0.01), respectively.The area under the concentration-time curve (AUC) 0-240 minutes in tears and corneas of the BTF-NM group was 7 488.90 (μg/g)·minute and 829.01 (μg/g)·minute, which was 7.2 and 52 times than that of the BTF-S group, respectively.No drugs were detected in the aqueous humor of the BTF-NM group and the BTF-S group. Conclusions:BTF-NM is an ideal agent with a simple preparing process, high drug encapsulation efficiency and small particle size.Compared with BTF suspension, BTF-NM can significantly improve the bioavailability of BTF in rabbit corneas.