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Junjie Zhang, Yanyan Xie, Tianyang Zhou, Jingguo Li, Jijun He, Huiyun Xia, Liya Wang; Development of natamycin-hydroxypropyl-beta-Cyclodextrin inclusion complex, ion-triggered in situ gel for sustained ocular delivery: in vitro, ex vivo evaluation and ocular pharmacokinetics study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2676. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Natamycin suspension eye drops (Nats) has been used to treat fungal keratitis. However, the water insolubility of natamycin (Nat) and the inherent barriers in cornea make it difficult for Nat to penetrate into eye. This study aimed to develop ion-sensitive Nat-hydroxypropyl-beta-Cyclodextrin inclusion complex (Nat-CD) in situ gels (Nat-CD-IG) to prolong ocular retention time and enhance cornea permeability
Nat-CD solution was first prepared by solvent evaporation method, and a series of formulations containing different ratios of methylcellulose and gellan gum in Nat-CD solution were prepared with 0.2%Nat content (w/v). Adhesive ability was evaluated. The release kinetics of Nat from the Nat-CD-IG in vitro was measured. The permeability of the Nat-CD-IG across the cornea of the rabbits ex vivo was studied by using side-by-side diffusion cells. The irritant of the Nat-CD-IG selected was evaluated using the Draize test. The ocular pharmacokinetics (PK) of Nat-CD-IG was evaluated after one single dose of 50μl was applied to the Japanese white rabbits with intact epithelium and deepithelium cornea , respectively. 5% Nats was used as the control group. The drug levels in tears, corneas and aqueous humors (AH) were determined by high performance liquid chromatography with UV-detector (HPLC). The data in tears, cornea and AH were conducted by PK software of DAS 2.1. The data at different time points were statistically analyzed by ANOVA.
The adhesive ability of Nat-CD-IG is more than 2-fold that of Nat-CD. The permeability of Nat across the cornea in Nat-CD-IG is significantly higher compared to Nats. The Nat-CD-IG demonstrates no irritation. The drug levels in tears, corneas and AH for Nat-CD-IG group were significantly higher than that for Nats and Nat-CD solution at the corresponding time points after one single dose of 50μl was applied to the rabbits with intact epithelium and deepithelium cornea, respectively. Nat-CD-IG significantly prolongs the Nat in eyes and enhances penetration into the cornea.
The developed Nat-CD-IG, ion-triggered in situ gel ocular system has great potential for sustained release of natamycin and penetration into cornea for treating fungal keratitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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