FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Get Full Text
Publication Date: 2020-04-16 PubMed ID: 32295599PubMed Central: PMC7160932DOI: 10.1186/s12917-020-02331-5Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.

References

This article includes 66 references
  1. Tuli SS. Fungal keratitis.. Clin Ophthalmol 2011;5:275-9.
    doi: 10.2147/OPTH.S10819pmc: PMC3065567pubmed: 21468333google scholar: lookup
  2. Thomas PA, Kaliamurthy J. Mycotic keratitis: epidemiology, diagnosis and management.. Clin Microbiol Infect 2013 Mar;19(3):210-20.
    doi: 10.1111/1469-0691.12126pubmed: 23398543google scholar: lookup
  3. Keay LJ, Gower EW, Iovieno A, Oechsler RA, Alfonso EC, Matoba A, Colby K, Tuli SS, Hammersmith K, Cavanagh D, Lee SM, Irvine J, Stulting RD, Mauger TF, Schein OD. Clinical and microbiological characteristics of fungal keratitis in the United States, 2001-2007: a multicenter study.. Ophthalmology 2011 May;118(5):920-6.
    doi: 10.1016/j.ophtha.2010.09.011pmc: PMC3673009pubmed: 21295857google scholar: lookup
  4. Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC. Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses.. Am J Vet Res 2006 Feb;67(2):296-301.
    doi: 10.2460/ajvr.67.2.296pubmed: 16454636google scholar: lookup
  5. Scotty NC. Equine keratomycosis. Clin Tech Equine Pract 2005;4(1):29–36.
    doi: 10.1053/j.ctep.2005.03.008google scholar: lookup
  6. Ledbetter EC. Antifungal Therapy in Equine Ocular Mycotic Infections.. Vet Clin North Am Equine Pract 2017 Dec;33(3):583-605.
    doi: 10.1016/j.cveq.2017.08.001pubmed: 28958862google scholar: lookup
  7. Clode AB, Matthews A. Diseases and surgery of the cornea. In: Gilger BC, editor. Equine ophthalmology. 2. Missouri: Elsevier Saunders; 2011. pp. 181–266.
  8. Mahdy RA, Nada WM, Wageh MM. Topical amphotericin B and subconjunctival injection of fluconazole (combination therapy) versus topical amphotericin B (monotherapy) in treatment of keratomycosis.. J Ocul Pharmacol Ther 2010 Jun;26(3):281-5.
    doi: 10.1089/jop.2010.0005pubmed: 20565316google scholar: lookup
  9. Smith KM, Pucket JD, Gilmour MA. Treatment of six cases of equine corneal stromal abscessation with intracorneal injection of 5% voriconazole solution.. Vet Ophthalmol 2014 Jul;17 Suppl 1:179-85.
    doi: 10.1111/vop.12136pubmed: 24387183google scholar: lookup
  10. Tsujita H, Plummer CE. Corneal stromal abscessation in two horses treated with intracorneal and subconjunctival injection of 1% voriconazole solution.. Vet Ophthalmol 2013 Nov;16(6):451-8.
    doi: 10.1111/vop.12014pubmed: 23228013google scholar: lookup
  11. Henriksen MDL, Andersen PH, Plummer CE, Mangan B, Brooks DE. Equine corneal stromal abscesses: an evolution in the understanding of pathogenesis and treatment during the past 30 years. Equine Vet Educ 2013;25(6):315–323.
    doi: 10.1111/j.2042-3292.2012.00440.xgoogle scholar: lookup
  12. Pearce JW, Giuliano EA, Moore CP. In vitro susceptibility patterns of Aspergillus and Fusarium species isolated from equine ulcerative keratomycosis cases in the midwestern and southern United States with inclusion of the new antifungal agent voriconazole.. Vet Ophthalmol 2009 Sep-Oct;12(5):318-24.
    doi: 10.1111/j.1463-5224.2009.00721.xpubmed: 19751493google scholar: lookup
  13. Al-Badriyeh D, Neoh CF, Stewart K, Kong DC. Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis.. Clin Ophthalmol 2010 May 6;4:391-405.
    pmc: PMC2866570pubmed: 20463910doi: 10.2147/opth.s6374google scholar: lookup
  14. Marangon FB, Miller D, Giaconi JA, Alfonso EC. In vitro investigation of voriconazole susceptibility for keratitis and endophthalmitis fungal pathogens.. Am J Ophthalmol 2004 May;137(5):820-5.
    doi: 10.1016/j.ajo.2003.11.078pubmed: 15126145google scholar: lookup
  15. Voelter-Ratson K, Monod M, Unger L, Spiess BM, Pot SA. Evaluation of the conjunctival fungal flora and its susceptibility to antifungal agents in healthy horses in Switzerland.. Vet Ophthalmol 2014 Jul;17 Suppl 1:31-6.
    doi: 10.1111/vop.12088pubmed: 23910390google scholar: lookup
  16. Lalitha P, Sun CQ, Prajna NV, Karpagam R, Geetha M, O'Brien KS, Cevallos V, McLeod SD, Acharya NR, Lietman TM. In vitro susceptibility of filamentous fungal isolates from a corneal ulcer clinical trial.. Am J Ophthalmol 2014 Feb;157(2):318-26.
    doi: 10.1016/j.ajo.2013.10.004pmc: PMC3896887pubmed: 24439440google scholar: lookup
  17. Sun CQ, Lalitha P, Prajna NV, Karpagam R, Geetha M, O'Brien KS, Oldenburg CE, Ray KJ, McLeod SD, Acharya NR, Lietman TM. Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis.. Ophthalmology 2014 Aug;121(8):1495-500.e1.
    doi: 10.1016/j.ophtha.2014.03.004pmc: PMC4122634pubmed: 24746358google scholar: lookup
  18. Rieke ER, Amaral J, Becerra SP, Lutz RJ. Sustained subconjunctival protein delivery using a thermosetting gel delivery system.. J Ocul Pharmacol Ther 2010 Feb;26(1):55-64.
    doi: 10.1089/jop.2009.0059pmc: PMC3096542pubmed: 20148655google scholar: lookup
  19. Gilger BC, Salmon JH, Wilkie DA, Cruysberg LP, Kim J, Hayat M, Kim H, Kim S, Yuan P, Lee SS, Harrington SM, Murray PR, Edelhauser HF, Csaky KG, Robinson MR. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.. Invest Ophthalmol Vis Sci 2006 Jun;47(6):2596-605.
    doi: 10.1167/iovs.05-1540pubmed: 16723476google scholar: lookup
  20. Ward MA, Georgiou TK. Thermoresponsive polymers for biomedical applications. Polymers 2011;3(3):1215–1242.
    doi: 10.3390/polym3031215google scholar: lookup
  21. Alhalafi AM. Applications of polymers in intraocular drug delivery systems.. Oman J Ophthalmol 2017 Jan-Apr;10(1):3-8.
    doi: 10.4103/0974-620X.200692pmc: PMC5338049pubmed: 28298856google scholar: lookup
  22. Jeong B, Bae YH, Kim SW. Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers.. J Control Release 2000 Jan 3;63(1-2):155-63.
    doi: 10.1016/S0168-3659(99)00194-7pubmed: 10640589google scholar: lookup
  23. Zentner GM, Rathi R, Shih C, McRea JC, Seo MH, Oh H, Rhee BG, Mestecky J, Moldoveanu Z, Morgan M, Weitman S. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs.. J Control Release 2001 May 14;72(1-3):203-15.
    doi: 10.1016/S0168-3659(01)00276-0pubmed: 11389999google scholar: lookup
  24. Cuming RS, Abarca EM, Duran S, Wooldridge AA, Stewart AJ, Ravis W, Babu RJ, Lin YJ, Hathcock T. Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses.. Invest Ophthalmol Vis Sci 2017 May 1;58(5):2746-2754.
    doi: 10.1167/iovs.16-20899pubmed: 28549089google scholar: lookup
  25. Fukuda T, Gouko R, Eitsuka T, Suzuki R, Takahashi K, Nakagawa K, Sugano E, Tomita H, Kiyono T. Human-Derived Corneal Epithelial Cells Expressing Cell Cycle Regulators as a New Resource for in vitro Ocular Toxicity Testing.. Front Genet 2019;10:587.
    doi: 10.3389/fgene.2019.00587pmc: PMC6646426pubmed: 31379915google scholar: lookup
  26. Han SB, Shin YJ, Hyon JY, Wee WR. Cytotoxicity of voriconazole on cultured human corneal endothelial cells.. Antimicrob Agents Chemother 2011 Oct;55(10):4519-23.
    doi: 10.1128/AAC.00569-11pmc: PMC3187006pubmed: 21768517google scholar: lookup
  27. Ko KY, Jeon HL, Kim J, Kim TS, Hong YH, Jeong MK, Park KH, Kim BH, Park S, Jang WH, Cho SA, An S, Cho AR, Yi JS, Kim JY, Kim H, Lee JK, Park KS. Two tiered approaches combining alternative test methods and minimizing the use of reconstructed human cornea-like epithelium tests for the evaluation of eye irritation potency of test chemicals.. Toxicol In Vitro 2020 Mar;63:104675.
    doi: 10.1016/j.tiv.2019.104675pubmed: 31648046google scholar: lookup
  28. Gao H, Pennesi M, Shah K, Qiao X, Hariprasad SM, Mieler WF, Wu SM, Holz ER. Safety of intravitreal voriconazole: electroretinographic and histopathologic studies.. Trans Am Ophthalmol Soc 2003;101:183-9; discussion 189.
    pmc: PMC1358987pubmed: 14971576
  29. Eaton JS, Miller PE, Bentley E, Thomasy SM, Murphy CJ. The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology.. J Ocul Pharmacol Ther 2017 Dec;33(10):718-734.
    doi: 10.1089/jop.2017.0108pubmed: 29239680google scholar: lookup
  30. Munger RJ. Veterinary ophthalmology in laboratory animal studies.. Vet Ophthalmol 2002 Sep;5(3):167-75.
    doi: 10.1046/j.1463-5224.2002.00243.xpubmed: 12236867google scholar: lookup
  31. Davis JL, Salmon JH, Papich MG. Pharmacokinetics of voriconazole after oral and intravenous administration to horses.. Am J Vet Res 2006 Jun;67(6):1070-5.
    doi: 10.2460/ajvr.67.6.1070pubmed: 16740104google scholar: lookup
  32. Gibaldi M, McNamara PJ. Apparent volumes of distribution and drug binding to plasma proteins and tissues.. Eur J Clin Pharmacol 1978 Jul 30;13(5):373-80.
    doi: 10.1007/BF00644611pubmed: 668796google scholar: lookup
  33. Kirbs C, Kluwe F, Drescher F, Lackner E, Matzneller P, Weiss J, Zeitlinger M, Kloft C. High voriconazole target-site exposure after approved sequence dosing due to nonlinear pharmacokinetics assessed by long-term microdialysis.. Eur J Pharm Sci 2019 Apr 1;131:218-229.
    doi: 10.1016/j.ejps.2019.02.001pubmed: 30731238google scholar: lookup
  34. Weiler S, Fiegl D, MacFarland R, Stienecke E, Bellmann-Weiler R, Dunzendorfer S, Joannidis M, Bellmann R. Human tissue distribution of voriconazole.. Antimicrob Agents Chemother 2011 Feb;55(2):925-8.
    doi: 10.1128/AAC.00949-10pmc: PMC3028808pubmed: 21078931google scholar: lookup
  35. Regnier A. Clinical pharmacology and therapeutics part 1: drug deliver. Vet Ophthalmol 2007;4:271–287.
  36. Maggs DJ. Ocular pharmacology and therapeutics. In: Maggs DJ, Miller PE, Ofri R, editors. Slatter's fundamentals of veterinary ophthalmology. 4. Saint Louis: W.B. Saunders; 2008. pp. 33–61.
  37. Wang LZ, Syn N, Li S, Barathi VA, Tong L, Neo J, Beuerman RW, Zhou L. The penetration and distribution of topical atropine in animal ocular tissues.. Acta Ophthalmol 2019 Mar;97(2):e238-e247.
    doi: 10.1111/aos.13889pubmed: 30259687google scholar: lookup
  38. Jinks MR, Fontenot RL, Wills RW, Betbeze CM. The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses.. Vet Ophthalmol 2018 Sep;21(5):498-506.
    doi: 10.1111/vop.12537pubmed: 29232029google scholar: lookup
  39. Schaefer E, Smith SM, Salmon J, Abbaraju S, Amin R, Weiss S, Grau U, Velagaleti P, Gilger B. Evaluation of Intracameral Pentablock Copolymer Thermosensitive Gel for Sustained Drug Delivery to the Anterior Chamber of the Eye.. J Ocul Pharmacol Ther 2017 Jun;33(5):353-360.
    doi: 10.1089/jop.2016.0181pubmed: 28300477google scholar: lookup
  40. Zhang L, Shen W, Luan J, Yang D, Wei G, Yu L, Lu W, Ding J. Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel.. Acta Biomater 2015 Sep;23:271-281.
    doi: 10.1016/j.actbio.2015.05.005pubmed: 26004219google scholar: lookup
  41. Tsai SH, Lin YC, Hsu HC, Chen YM. Subconjunctival Injection of Fluconazole in the Treatment of Fungal Alternaria Keratitis.. Ocul Immunol Inflamm 2016;24(1):103-6.
    doi: 10.3109/09273948.2014.916308pubmed: 24830382google scholar: lookup
  42. Voss K, Falke K, Bernsdorf A, Grabow N, Kastner C, Sternberg K, Minrath I, Eickner T, Wree A, Schmitz KP, Guthoff R, Witt M, Hovakimyan M. Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment.. J Control Release 2015 Sep 28;214:1-11.
    doi: 10.1016/j.jconrel.2015.06.035pubmed: 26160303google scholar: lookup
  43. Jiang X, Lv H, Qiu W, Liu Z, Li X, Wang W. Efficiency and safety of subconjunctival injection of anti-VEGF agent - bevacizumab - in treating dry eye.. Drug Des Devel Ther 2015;9:3043-50.
    pmc: PMC4472070pubmed: 26109847doi: 10.2147/dddt.s85529google scholar: lookup
  44. Gilmour MA. Subconjunctival voriconazole for the treatment of mycotic keratitis in a horse. Equine Vet Educ 2012;24(10):489–492.
    doi: 10.1111/j.2042-3292.2011.00319.xgoogle scholar: lookup
  45. Xu X, Yu J, Shi H, Zhang J, Li X. Prevention of corneal neovascularization by subconjunctival injection of avastin® loaded thermosensitive hydrogels in rabbit model.. Int J Pharm 2018 Dec 1;552(1-2):164-170.
    doi: 10.1016/j.ijpharm.2018.09.017pubmed: 30217769google scholar: lookup
  46. 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.
    doi: 10.1208/s12248-019-0326-xpubmed: 31020458google scholar: lookup
  47. Short BG. Safety evaluation of ocular drug delivery formulations: techniques and practical considerations.. Toxicol Pathol 2008 Jan;36(1):49-62.
    doi: 10.1177/0192623307310955pubmed: 18337221google scholar: lookup
  48. Dastjerdi MH, Sadrai Z, Saban DR, Zhang Q, Dana R. Corneal penetration of topical and subconjunctival bevacizumab.. Invest Ophthalmol Vis Sci 2011 Nov 7;52(12):8718-23.
    doi: 10.1167/iovs.11-7871pmc: PMC3230312pubmed: 22003112google scholar: lookup
  49. Weijtens O, Feron EJ, Schoemaker RC, Cohen AF, Lentjes EG, Romijn FP, van Meurs JC. High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection.. Am J Ophthalmol 1999 Aug;128(2):192-7.
    doi: 10.1016/S0002-9394(99)00129-4pubmed: 10458175google scholar: lookup
  50. Yoo AR, Chung SK. Effects of subconjunctival tocilizumab versus bevacizumab in treatment of corneal neovascularization in rabbits.. Cornea 2014 Oct;33(10):1088-94.
    doi: 10.1097/ICO.0000000000000220pubmed: 25119962google scholar: lookup
  51. Gum GG, Mackay EO. Physiology of the Eye. In: Gelatt KN, editor. Essentials of Veterinary Ophthalmology. 5th edition. Ames (IA): Wiley-Blackwell; 2013. p. 171–207.
  52. Barar J, Aghanejad A, Fathi M, Omidi Y. Advanced drug delivery and targeting technologies for the ocular diseases.. Bioimpacts 2016;6(1):49-67.
    doi: 10.15171/bi.2016.07pmc: PMC4916551pubmed: 27340624google scholar: lookup
  53. Gough G, Szapacs M, Shah T, Clements P, Struble C, Wilson R. Ocular tissue distribution and pharmacokinetic study of a small 13kDa domain antibody after intravitreal, subconjuctival and eye drop administration in rabbits.. Exp Eye Res 2018 Feb;167:14-17.
    doi: 10.1016/j.exer.2017.10.021pubmed: 29074387google scholar: lookup
  54. Passler NH, Chan HM, Stewart AJ, Duran SH, Welles EG, Lin HC, Ravis WR. Distribution of voriconazole in seven body fluids of adult horses after repeated oral dosing.. J Vet Pharmacol Ther 2010 Feb;33(1):35-41.
    doi: 10.1111/j.1365-2885.2009.01099.xpubmed: 20444023google scholar: lookup
  55. Gilger BC, Reeves KA, Salmon JH. Ocular parameters related to drug delivery in the canine and equine eye: aqueous and vitreous humor volume and scleral surface area and thickness.. Vet Ophthalmol 2005 Jul-Aug;8(4):265-9.
    doi: 10.1111/j.1463-5224.2005.00401.xpubmed: 16008707google scholar: lookup
  56. Conrad JM, Robinson JR. Mechanisms of anterior segment absorption of pilocarpine following subconjunctival injection in albino rabbits.. J Pharm Sci 1980 Aug;69(8):875-84.
    doi: 10.1002/jps.2600690806pubmed: 7400929google scholar: lookup
  57. Yavuz B, Kompella UB. Ocular Drug Delivery.. Handb Exp Pharmacol 2017;242:57-93.
    doi: 10.1007/164_2016_84pubmed: 27783270google scholar: lookup
  58. Kang-Mieler JJ, Dosmar E, Liu W, Mieler WF. Extended ocular drug delivery systems for the anterior and posterior segments: biomaterial options and applications.. Expert Opin Drug Deliv 2017 May;14(5):611-620.
    pubmed: 27551742doi: 10.1080/17425247.2016.1227785google scholar: lookup
  59. Theuretzbacher U, Ihle F, Derendorf H. Pharmacokinetic/pharmacodynamic profile of voriconazole.. Clin Pharmacokinet 2006;45(7):649-63.
    doi: 10.2165/00003088-200645070-00002pubmed: 16802848google scholar: lookup
  60. Verweij PE, Chowdhary A, Melchers WJ, Meis JF. Azole Resistance in Aspergillus fumigatus: Can We Retain the Clinical Use of Mold-Active Antifungal Azoles?. Clin Infect Dis 2016 Feb 1;62(3):362-8.
    doi: 10.1093/cid/civ885pmc: PMC4706635pubmed: 26486705google scholar: lookup
  61. Warris A. Azole-resistant aspergillosis.. J Infect 2015 Jun;71 Suppl 1:S121-5.
    doi: 10.1016/j.jinf.2015.04.023pubmed: 25917808google scholar: lookup
  62. Molokhia SA, Thomas SC, Garff KJ, Mandell KJ, Wirostko BM. Anterior eye segment drug delivery systems: current treatments and future challenges.. J Ocul Pharmacol Ther 2013 Mar;29(2):92-105.
    doi: 10.1089/jop.2012.0241pubmed: 23485091google scholar: lookup
  63. Ghate D, Brooks W, McCarey BE, Edelhauser HF. Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry.. Invest Ophthalmol Vis Sci 2007 May;48(5):2230-7.
    doi: 10.1167/iovs.06-0954pubmed: 17460284google scholar: lookup
  64. Cheruvu NP, Kompella UB. Bovine and porcine transscleral solute transport: influence of lipophilicity and the Choroid-Bruch's layer.. Invest Ophthalmol Vis Sci 2006 Oct;47(10):4513-22.
    doi: 10.1167/iovs.06-0404pmc: PMC3324974pubmed: 17003447google scholar: lookup
  65. Abarca EM, Salmon JH, Gilger BC. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model.. J Ocul Pharmacol Ther 2013 Oct;29(8):715-22.
    doi: 10.1089/jop.2013.0063pubmed: 23822159google scholar: lookup
  66. Khoschsorur G, Fruehwirth F, Zelzer S. Isocratic high-performance liquid chromatographic method with ultraviolet detection for simultaneous determination of levels of voriconazole and itraconazole and its hydroxy metabolite in human serum.. Antimicrob Agents Chemother 2005 Aug;49(8):3569-71.
    doi: 10.1128/AAC.49.8.3569-3571.2005pmc: PMC1196257pubmed: 16048987google scholar: lookup

Citations

This article has been cited 3 times.
  1. 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).
    doi: 10.3390/polym14163368pubmed: 36015626google scholar: lookup
  2. Allyn MM, Luo RH, Hellwarth EB, Swindle-Reilly KE. Considerations for Polymers Used in Ocular Drug Delivery. Front Med (Lausanne) 2021;8:787644.
    doi: 10.3389/fmed.2021.787644pubmed: 35155469google scholar: lookup
  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).
    doi: 10.3390/gels9120933pubmed: 38131919google scholar: lookup
Subscribe to our newsletter
Join 99,911 horse owners like you who receive our email updates on horse health and nutrition.