Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses.
Abstract: 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). 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. 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. Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo.
Publication Date: 2017-05-27 PubMed ID: 28549089DOI: 10.1167/iovs.16-20899Google Scholar: Lookup
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- Journal Article
Summary
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This research investigates the development and effectiveness of a slow-release, voriconazole-containing gel for subconjunctival injection in horses, to assist in the treatment of keratomycosis. It tests the gel’s release rate, its permeation through the cornea and sclera, its antifungal activity, and its injection characteristics, suggesting promising potential for the treatment.
Investigated Gel and Test Procedures
- The gel investigated was a Voriconazole-Containing Thermogel (VCT) – a polymer-based composition designed to solidify at body temperature, allowing for sustained release of the drug voriconazole.
- The researchers developed two concentrations of the gel (0.3% and 1.5% voriconazole) and tested its in vitro release rates over 28 days.
- The permeability of the thermogel across the cornea and sclera were examined using a Franz cell diffusion chamber.
- The gel’s antifungal activity was tested via the agar disk diffusion method.
- The shape of the gel post-injection was investigated using equine eyes ex vivo, while the gel’s injection performance and any potential adverse effects were tested in vivo, on a live horse.
Findings on Release and Permeation
- The VCT released voriconazole consistently over 21 days, following first-order kinetics – a process where the rate of release is proportional to the concentration of the gel.
- The voriconazole diffused through both the cornea and the sclera – the protective outer layers of the eye – with greater permeation observed through the sclera.
Anti-fungal Activity and Gel Injection
- The voriconazole released from the 1.5% thermogel showed antifungal activity in tests.
- The VCT could be easily injected into the dorsal Subconjunctival Space (SCS – a potential space between the conjunctiva and episclera) and formed a discrete gel deposit, which is ideal for the gradual release of medication.
- In vivo, the gel was injected easily and found not to induce any adverse reactions in the horse.
Research Implications
- The research concludes that VCTs show great potential for the treatment of keratomycosis – a fungal eye infection commonly found in horses.
- Further research is required to test their performance in vivo and in actual patient scenarios.
Cite This Article
APA
Cuming RS, Abarca EM, Duran S, Wooldridge AA, Stewart AJ, Ravis W, Babu RJ, Lin YJ, Hathcock T.
(2017).
Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses.
Invest Ophthalmol Vis Sci, 58(5), 2746-2754.
https://doi.org/10.1167/iovs.16-20899 Publication
Researcher Affiliations
- J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States.
- J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States 2Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States.
- J. T. Vaughan Large Animal Teaching Hospital, Auburn University, Auburn, Alabama, United States.
- University of Queensland, School of Veterinary Science, Gatton, Queensland, Australia.
- Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, United States.
- Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, United States.
- Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, United States.
- Department of Pathobiology, Auburn University, Auburn, Alabama, United States.
MeSH Terms
- Animals
- Antifungal Agents / chemistry
- Antifungal Agents / pharmacokinetics
- Antifungal Agents / pharmacology
- Aspergillus flavus / drug effects
- Chromatography, High Pressure Liquid
- Conjunctiva / drug effects
- Cornea / metabolism
- Delayed-Action Preparations
- Disease Models, Animal
- Drug Carriers
- Eye Infections, Fungal / drug therapy
- Gels
- Horses
- Injections, Intraocular
- Polyesters / chemistry
- Polyethylene Glycols / chemistry
- Sclera / metabolism
- Temperature
- Tissue Distribution
- Voriconazole / chemistry
- Voriconazole / pharmacokinetics
- Voriconazole / pharmacology
Citations
This article has been cited 5 times.- Wu KY, Joly-Chevrier M, Akbar D, Tran SD. Overcoming Treatment Challenges in Posterior Segment Diseases with Biodegradable Nano-Based Drug Delivery Systems.. Pharmaceutics 2023 Mar 29;15(4).
- Ahmed S, Amin MM, Sayed S. Ocular Drug Delivery: a Comprehensive Review.. AAPS PharmSciTech 2023 Feb 14;24(2):66.
- Gu W, Fan R, Quan J, Cheng Y, Wang S, Zhang H, Zheng A, Song S. Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA-PEG-PLGA Triblock Copolymer Blending for GBM Treatment.. Polymers (Basel) 2022 Aug 18;14(16).
- Mora-Pereira M, Abarca EM, Duran S, Ravis W, McMullen RJ Jr, Fischer BM, Lee YP, Wooldridge AA. Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies.. BMC Vet Res 2020 Apr 16;16(1):115.
- Chan PS, Xian JW, Li Q, Chan CW, Leung SSY, To KKW. Biodegradable Thermosensitive PLGA-PEG-PLGA Polymer for Non-irritating and Sustained Ophthalmic Drug Delivery.. AAPS J 2019 Apr 24;21(4):59.
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