Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses.

Autor:	Cuming RS; J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States., Abarca EM; J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States 2Vetsuisse Faculty, University of Bern, Bern, Switzerland., Duran S; J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States., Wooldridge AA; J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States., Stewart AJ; University of Queensland, School of Veterinary Science, Gatton, Queensland, Australia., Ravis W; Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, United States., Babu RJ; Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, United States., Lin YJ; Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, United States., Hathcock T; Department of Pathobiology, Auburn University, Auburn, Alabama, United States.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2017 May 01; Vol. 58 (5), pp. 2746-2754.
DOI:	10.1167/iovs.16-20899
Abstrakt:	Purpose: To determine in vitro release profiles, transcorneal permeation, and ocular injection characteristics of a voriconazole-containing thermogel suitable for injection into the subconjunctival space (SCS). Methods: In vitro release rate of voriconazole (0.3% and 1.5%) from poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermogel was determined for 28 days. A Franz cell diffusion chamber was used to evaluate equine transcorneal and transscleral permeation of voriconazole (1.5% topical solution, 0.3% and 1.5% voriconazole-thermogel) for 24 hours. Antifungal activity of voriconazole released from the 1.5% voriconazole-thermogel was determined via the agar disk diffusion method. Ex vivo equine eyes were injected with liquid voriconazole-thermogel (4°C). Distension of the SCS was assessed ultrasonographically and macroscopically. SCS voriconazole-thermogel injections were performed in a horse 1 week and 2 hours before euthanasia and histopathologic analysis of ocular tissues performed. Results: Voriconazole was released from the PLGA-PEG-PLGA thermogel for more than 21 days in all groups. Release followed first-order kinetics. Voriconazole diffused through the cornea and sclera in all groups. Permeation was greater through the sclerae than corneas. Voriconazole released from the 1.5% voriconazole-thermogel showed antifungal activity in vitro. Voriconazole-thermogel was easily able to be injected into the dorsal SCS where it formed a discrete gel deposit. Voriconazole-thermogel was easily injected in vivo and did not induce any adverse reactions. Conclusions: Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo.
Databáze:	MEDLINE
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