Sustained-Release Voriconazole-Thermogel for Subconjunctival Injection in Horses: Ocular Toxicity and in-vivo Studies
Type of DegreeMaster's Thesis
General Veterinary Medicine
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Subconjunctival (SC) injection of a thermosensitive voriconazole-hydrogel poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) may allow for sustained delivery of voriconazole to the anterior segment of the eye. Equine corneas were exposed to voriconazole thermogel (1 and 5 mg), plain thermogel and phosphate buffered solution (PBS) using a Franz Cell diffusion chamber, and analyzed by histology. At 2 hours, no difference was found between treatments for corneal epithelial and stromal thickness. Artifactss at longer time points precluded analysis. Six horses received 1% topical voriconazole or 1.7% subconjunctival (SC) voriconazole-thermogel. Using a Hackett-McDonald scoring system for inflammation, there were changes in conjunctival swelling and congestion following injection, but no signs of ocular pain. On day 2, drug concentration in tears was not different between groups. For the thermogel group, voriconazole was not detected in the aqueous humor (AH). Three horses received a 1.7% SC voriconazole-thermogel injection 48 and 2 hours prior euthanasia; voriconazole concentrations were above the target minimum inhibitory concentration (MIC) in the tissues of the anterior segment of the eye. Voriconazole-containing thermogel was easy and safe to administer in horses with no adverse effects. The thermogel provided sustained release of voriconazole, and the high lipophilicity and volume of distribution of the drug enhanced the distribution to the ocular tissues, thus making this drug delivery system of potential importance for the treatment of equine keratomycosis.