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Home / Equine Research Bank / BMC Vet Res / Sustained-release voriconazole-thermogel for subconjunctival...
BMC veterinary research2020; 16(1); 115; doi: 10.1186/s12917-020-02331-5

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies.

Abstract: Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrations in the anterior segment and clinical effects after SCo injections of voriconazole-containing thermogel: poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) in healthy equine eyes. Results: Voriconazole aqueous humor (AH) and tear concentrations were compared between 6 horses, receiving 1% voriconazole applied topically (0.2 mL, q4h) (Vori-Top) or 1.7% voriconazole-thermogel (0.3 mL) injected SCo (Vori-Gel). For the Vori-Gel group, voriconazole concentrations were measured in AH and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group. Ocular inflammation was assessed weekly (Vori-Gel) using the modified Hackett-McDonald scoring system. Ocular tissue concentrations of voriconazole following SCo 1.7% voriconazole-thermogel (0.3 mL) injections were evaluated post euthanasia in 6 additional horses at 3 different time points. Three horses received bilateral injections at 2 h (n = 3, right eye (OD)) and 48 h (n = 3, left eye (OS)) prior to euthanasia, and 3 horses were injected unilaterally (OS), 7 days prior to euthanasia. Voriconazole-thermogel was easily injected and well tolerated in all cases, with no major adverse effects. On day 2, drug concentrations in tears were higher in the Vori-Top, but not statistically different from Vori-Gel groups. For the Vori-Gel group, voriconazole was non-quantifiable in the AH at any time point. Total voriconazole concentrations in the cornea were above 0.5 μg/g (the target minimum inhibitory concentration (MIC) for Aspergillus sp.) for up to 48 h; however, concentrations were below this MIC at 7 days post treatment. Conclusions: Voriconazole-thermogel was easily and safely administered to horses, and provided 48 h of sustained release of voriconazole into the cornea. This drug delivery system warrants further clinical evaluation.
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Publication Date: 2020-04-16 PubMed ID: 32295599PubMed Central: PMC7160932DOI: 10.1186/s12917-020-02331-5Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research focuses on a new method to effectively treat a common, sight-threatening condition in horses called keratomycosis, using voriconazole-thermogel via subconjunctival injections. It explores the related ocular toxicity and in vivo trials.

Objective of the Research

  • The study primarily aims to evaluate the impact and efficacy of voriconazole-containing thermogel when injected into the subconjunctival (SCo) space of healthy equine eyes. It also investigates how effectively these injections could provide sustained drug release.
  • Part of the study is to analyse the voriconazole concentrations in the eyes’ anterior segment, which includes the cornea, iris, and lens, following the SCo injections.

Methodology

  • The study compared voriconazole levels in the aqueous humor (the clear fluid in the front of the eye) and tears between 6 horses. One group had 1% voriconazole applied topically (Vori-Top), whereas the other group had 1.7% voriconazole-thermogel injected SCo (Vori-Gel).
  • For the Vori-Gel group, voriconazole concentrations were measured in the aqueous humor and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group.
  • Ocular inflammation was assessed weekly in the Vori-Gel group using the modified Hackett-McDonald scoring system.
  • Ocular tissue concentrations of voriconazole post injections were evaluated in 6 different horses following their euthanasia, at three different time intervals.

Results

  • Voriconazole-thermogel was easily injected and well accepted in all cases, with no significant adverse effects observed.
  • On day 2, drug concentrations in tears were higher in the Vori-Top group, but not statistically different from the Vori-Gel.
  • For the Vori-Gel group, voriconazole could not be quantified in the aqueous humor at any time.
  • Voriconazole concentrations in the cornea were above the target minimum inhibitory concentration for Aspergillus (a common fungal organism causing keratomycosis) for up to 48 hours. However, these concentrations were below the target minimum inhibitory concentration at day 7 post treatment.

Conclusion

  • The voriconazole-thermogel injections effectively and safely provided 48 hours of sustained voriconazole release into the cornea, demonstrating its potential as an effective treatment method.
  • Based on the study findings, it recommends further clinical evaluation of this drug delivery system.

Cite This Article

APA
Mora-Pereira M, Abarca EM, Duran S, Ravis W, McMullen RJ, Fischer BM, Lee YP, Wooldridge AA. (2020). Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies. BMC Vet Res, 16(1), 115. https://doi.org/10.1186/s12917-020-02331-5

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 16
Issue: 1
Pages: 115
PII: 115

Researcher Affiliations

Mora-Pereira, Mariano
  • J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, AL, USA.
Abarca, Eva M
  • J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, AL, USA. e.abarca@arsveterinaria.es.
Duran, Sue
  • J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, AL, USA.
Ravis, William
  • Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA.
McMullen, Richard J
  • J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, AL, USA.
Fischer, Britta M
  • J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, AL, USA.
Lee, Yann-Huei Phillip
  • Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA.
Wooldridge, Anne A
  • J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, AL, USA.

MeSH Terms

  • Administration, Topical
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects
  • Antifungal Agents / pharmacokinetics
  • Aqueous Humor / chemistry
  • Cornea / chemistry
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Delayed-Action Preparations / pharmacokinetics
  • Gels / chemistry
  • Horses
  • Injections / methods
  • Injections / veterinary
  • Polymers / chemistry
  • Tears / chemistry
  • Voriconazole / administration & dosage
  • Voriconazole / adverse effects
  • Voriconazole / pharmacokinetics

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 3 times.
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  2. Allyn MM, Luo RH, Hellwarth EB, Swindle-Reilly KE. Considerations for Polymers Used in Ocular Drug Delivery. Front Med (Lausanne) 2021;8:787644.
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  3. Rakhmetova A, Yi Z, Sarmout M, Koole LH. Sustained Release of Voriconazole Using 3D-Crosslinked Hydrogel Rings and Rods for Use in Corneal Drug Delivery. Gels 2023 Nov 28;9(12).
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