Development of a sustained-release voriconazole-containing thermogel for subconjunctival injection in horses
Type of DegreeMaster's Thesis
General Veterinary Medicine
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Subconjunctival administration of a slow-release, voriconazole-containing thermogel may allow for sustained delivery of voriconazole to the cornea and anterior chamber. Thermogel development consisted of four experiments. i) In vitro voriconazole release. Liquid (4°C) poly (DL-lactide-co-glycolide-b-ethylene glycol-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) (+0mg, 1mg and 5mg voriconazole) was placed in glass vials at 34.5°C to induce gelation. Physiological buffered saline (PBS) was added and samples collected for 28 days. ii) In vitro permeation. Permeation of voriconazole (1.5% solution, 0.3% and 1.5% thermogel) through equine corneas and sclerae was determined using a Franz Cell diffusion chamber. PBS was collected for 24 hours and voriconazole concentrations measured via high performance liquid chromatography (HPLC). iii) Characterization of thermogel subconjunctival space (SCS) injection. Ten normothermic ex vivo equine eyes were injected with liquid thermogel (4°C). iv) In vivo ocular toxicity. SCS thermogel injections were performed in a horse 1 week and 2 hours pre-euthanasia. Toxicity was evaluated via ocular inflammatory scores and histopathology. Voriconazole was released from the PLGA-PEG-PLGA thermogel in vitro and diffused through the cornea and sclera in effective concentrations. The thermogel formed a discrete gel deposit in the dorsal bulbar SCS and did not induce adverse reactions in vivo. Voriconazole-containing thermogels have potential application in treatment of equine keratomycosis.