FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Int J Mol Sci / PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeut...
International journal of molecular sciences2023; 24(6); 5735; doi: 10.3390/ijms24065735

PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses.

Abstract: The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 °C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased significantly by the value of 0.3% compared to previous weeks. In all of the cases, the TPU/PLA doped with 12 mg of the CsA platform effectively reduced the clinical symptoms of keratitis, leading to the complete remission of the corneal opacity and infiltration four weeks post-injection. The results from this study showed that the PLDLA/TPU matrix enriched with the CsA platform was well tolerated by the equine model and effective in treating superficial and mid-stromal IMMK.
Get Full Text
Publication Date: 2023-03-17 PubMed ID: 36982806PubMed Central: PMC10057311DOI: 10.3390/ijms24065735Google 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.

This study explores the utility and effectiveness of a chemical matrix, constructed using polymers and fortified with a therapeutic compound, Cyclosporine A (CsA), for treating immune-mediated keratitis (IMMK), a common eye disorder in horses. The research showed that the developed matrix released the therapeutic compound at an effective rate and reduced the symptoms of keratitis in horses, leading to complete remission.

Overview of Research Methods

This research involved several comprehensive and systematic experiments:

  • The matrix for drug delivery was constructed using thermoplastic polyurethane (TPU) polymer and a copolymer, both of which have been previously demonstrated to be biodegradable and biocompatible.
  • The researchers then further enriched this matrix construction with Cyclosporine A (CsA), a potent immunosuppressant drug traditionally used in organ transplantation and various autoimmune disorders.
  • The team conducted an in vitro (lab environment) evaluation of the CsA release rate from the matrix over a set period and also inspected the degradation of the polymer blend.
  • To replicate the natural and physiological environment, the researchers used Simulated Tear Fluid (STF) kept at a standard body temperature of 37°C.
  • In the animal model phase, the researchers injected the novel therapeutic matrix subconjunctivally (under the conjunctiva, the clear tissue covering the white part of the eye) into horses diagnosed with superficial and mid-stromal IMMK.

Outcomes of the Study and Further Findings

The findings from this study were promising:

  • The CsA release rate increased significantly by the fifth week, displaying a rise of 0.3%, suggesting that the matrix provided a stable and consistent medium for the drug to disperse from.
  • Post-injection assessments exhibited a considerable reduction in the symptoms of keratitis in all tested horses, eventually leading to complete remission of corneal opacity and infiltration.
  • Importantly, the PLDLA/TPU matrix enhanced with CsA was well tolerated by the horses and was shown to be effective in treating the diagnosed IMMK.

This research provides support for using biodegradable polymer matrices as drug delivery platforms for the controlled release of therapeutic agents, like CsA, in horses. The findings could influence the development of effective treatments for other ocular disorders in animals.

Cite This Article

APA
Padjasek M, Cisło-Sankowska A, Lis-Bartos A, Qasem B, Marycz K. (2023). PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses. Int J Mol Sci, 24(6), 5735. https://doi.org/10.3390/ijms24065735

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 24
Issue: 6
PII: 5735

Researcher Affiliations

Padjasek, Martyna
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
  • International Institute of Translational Medicine, Jesionowa 11 St., 55-124 Malin, Poland.
Cisło-Sankowska, Anna
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
  • International Institute of Translational Medicine, Jesionowa 11 St., 55-124 Malin, Poland.
Lis-Bartos, Anna
  • Department of Biomaterials and Composites, Faculty of Material Science and Ceramics, AGH University of Science and Technology, Aleja Adama Mickiewicza 30, 30-059 Krakow, Poland.
Qasem, Badr
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
  • International Institute of Translational Medicine, Jesionowa 11 St., 55-124 Malin, Poland.
Marycz, Krzysztof
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
  • International Institute of Translational Medicine, Jesionowa 11 St., 55-124 Malin, Poland.

MeSH Terms

  • Horses
  • Animals
  • Cyclosporine / therapeutic use
  • Polyurethanes
  • Keratitis / drug therapy
  • Keratitis / veterinary

Grant Funding

  • 2021/13/134 / Wrocu0142aw University of Environmental and Life Sciences

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 30 references
  1. Matthews AG. Nonulcerative Keratopathies in the Horse. Equine Vet. Educ. 2000;12:271–278.
    doi: 10.1111/j.2042-3292.2000.tb00057.xgoogle scholar: lookup
  2. Matthews A, Gilger BC. Equine immune-mediated keratopathies.. Vet Ophthalmol 2009 Nov-Dec;12 Suppl 1:10-6.
    doi: 10.1111/j.1463-5224.2009.00740.xpubmed: 19891646google scholar: lookup
  3. Pate DO, Clode AB, Olivry T, Cullen JM, Salmon JH, Gilger BC. Immunohistochemical and immunopathologic characterization of superficial stromal immune-mediated keratitis in horses.. Am J Vet Res 2012 Jul;73(7):1067-73.
    doi: 10.2460/ajvr.73.7.1067pubmed: 22738059google scholar: lookup
  4. Robinson MR, Whitcup SM. Pharmacologic and clinical profile of dexamethasone intravitreal implant.. Expert Rev Clin Pharmacol 2012 Nov;5(6):629-47.
    doi: 10.1586/ecp.12.55pubmed: 23234323google scholar: lookup
  5. Ledbetter EC, Irby NL. Laser scanning in vivo confocal microscopic characterization of equine immune-mediated keratitis.. Vet Ophthalmol 2020 Jan;23(1):4-15.
    doi: 10.1111/vop.12677pubmed: 31050168google scholar: lookup
  6. Gilger BC, Michau TM, Salmon JH. Immune-mediated keratitis in horses: 19 cases (1998-2004).. Vet Ophthalmol 2005 Jul-Aug;8(4):233-9.
    doi: 10.1111/j.1463-5224.2005.00393.xpubmed: 16008702google scholar: lookup
  7. Gilger BC, Stoppini R, Wilkie DA, Clode AB, Pinto NH, Hempstead J, Gerding J, Salmon JH. Treatment of immune-mediated keratitis in horses with episcleral silicone matrix cyclosporine delivery devices.. Vet Ophthalmol 2014 Jul;17 Suppl 1:23-30.
    doi: 10.1111/vop.12087pubmed: 23910236google scholar: lookup
  8. Matthews AG. Cyclosporine A and the equine cornea.. Equine Vet J 1995 Sep;27(5):320-1.
    doi: 10.1111/j.2042-3306.1995.tb04063.xpubmed: 8654343google scholar: lookup
  9. Gratzek AT, Kaswan RL, Martin CL, Champagne ES, White SL. Ophthalmic cyclosporine in equine keratitis and keratouveitis: 11 cases.. Equine Vet J 1995 Sep;27(5):327-33.
    doi: 10.1111/j.2042-3306.1995.tb04066.xpubmed: 8654346google scholar: lookup
  10. Padjasek M, Qasem B, Cisło-Pakuluk A, Marycz K. Cyclosporine A Delivery Platform for Veterinary Ophthalmology-A New Concept for Advanced Ophthalmology.. Biomolecules 2022 Oct 20;12(10).
    doi: 10.3390/biom12101525pmc: PMC9599649pubmed: 36291734google scholar: lookup
  11. Faulds D, Goa KL, Benfield P. Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders.. Drugs 1993 Jun;45(6):953-1040.
    doi: 10.2165/00003495-199345060-00007pubmed: 7691501google scholar: lookup
  12. Patocka J, Nepovimova E, Kuca K, Wu W. Cyclosporine A: Chemistry and Toxicity - A Review.. Curr Med Chem 2021;28(20):3925-3934.
    doi: 10.2174/0929867327666201006153202pubmed: 33023428google scholar: lookup
  13. Chang-Lin JE, Burke JA, Peng Q, Lin T, Orilla WC, Ghosn CR, Zhang KM, Kuppermann BD, Robinson MR, Whitcup SM, Welty DF. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes.. Invest Ophthalmol Vis Sci 2011 Jun 28;52(7):4605-9.
    doi: 10.1167/iovs.10-6387pubmed: 21421864google scholar: lookup
  14. Ghosn CR, Li Y, Orilla WC, Lin T, Wheeler L, Burke JA, Robinson MR, Whitcup SM. Treatment of experimental anterior and intermediate uveitis by a dexamethasone intravitreal implant.. Invest Ophthalmol Vis Sci 2011 May 2;52(6):2917-23.
    doi: 10.1167/iovs.10-5939pubmed: 21273539google scholar: lookup
  15. Lowder C, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, Li XY, Cui H, Whitcup SM. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis.. Arch Ophthalmol 2011 May;129(5):545-53.
    doi: 10.1001/archophthalmol.2010.339pubmed: 21220619google scholar: lookup
  16. Braus BK, Miller I, Kummer S, Kleinwort KJH, Hirmer S, Hauck SM, McMullen RJ Jr, Kerschbaumer M, Deeg CA. Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK).. Vet Immunol Immunopathol 2017 May;187:48-54.
    doi: 10.1016/j.vetimm.2017.04.002pubmed: 28494929google scholar: lookup
  17. Patel D, Wairkar S. Recent advances in cyclosporine drug delivery: challenges and opportunities.. Drug Deliv Transl Res 2019 Dec;9(6):1067-1081.
    doi: 10.1007/s13346-019-00650-1pubmed: 31144214google scholar: lookup
  18. Kaswan RL, Salisbury MA, Ward DA. Spontaneous canine keratoconjunctivitis sicca. A useful model for human keratoconjunctivitis sicca: treatment with cyclosporine eye drops.. Arch Ophthalmol 1989 Aug;107(8):1210-6.
    doi: 10.1001/archopht.1989.01070020276038pubmed: 2757551google scholar: lookup
  19. Kaswan RL, Salisbury MA. A new perspective on canine keratoconjunctivitis sicca. Treatment with ophthalmic cyclosporine.. Vet Clin North Am Small Anim Pract 1990 May;20(3):583-613.
    doi: 10.1016/S0195-5616(90)50052-2pubmed: 2194349google scholar: lookup
  20. Williams DL, Hoey AJ, Smitherman P. Comparison of topical cyclosporin and dexamethasone for the treatment of chronic superficial keratitis in dogs.. Vet Rec 1995 Dec 16;137(25):635-9.
    pubmed: 8693674
  21. McMullen RJ Jr, Fischer BM. Medical and Surgical Management of Equine Recurrent Uveitis.. Vet Clin North Am Equine Pract 2017 Dec;33(3):465-481.
    doi: 10.1016/j.cveq.2017.07.003pubmed: 28985983google scholar: lookup
  22. Bauer BS. Ocular Pathology.. Vet Clin North Am Equine Pract 2015 Aug;31(2):425-48.
    doi: 10.1016/j.cveq.2015.04.001pubmed: 26210955google scholar: lookup
  23. Robin M. Immune-Mediated Disorders of the Equine Eye: Part 1—The Cornea. UK-Vet. Equine. 2020;4:176–182.
    doi: 10.12968/ukve.2020.4.6.176google scholar: lookup
  24. Mi HY, Salick MR, Jing X, Jacques BR, Crone WC, Peng XF, Turng LS. Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding.. Mater Sci Eng C Mater Biol Appl 2013 Dec 1;33(8):4767-76.
    doi: 10.1016/j.msec.2013.07.037pmc: PMC4554542pubmed: 24094186google scholar: lookup
  25. Hentschel T, Münstedt H. Thermoplastic polyurethane--the material used for the Erlanger silver catheter.. Infection 1999;27 Suppl 1:S43-5.
    doi: 10.1007/BF02561617pubmed: 10379443google scholar: lookup
  26. Diao H, Si Y, Zhu A, Ji L, Shi H. Surface modified nano-hydroxyapatite/poly(lactide acid) composite and its osteocyte compatibility.. Mater Sci Eng C Mater Biol Appl 2012 Oct 1;32(7):1796-1801.
    doi: 10.1016/j.msec.2012.04.065pubmed: 34062658google scholar: lookup
  27. Kong Y, Yuan J, Qiu J. Preparation and Characterization of Aligned Carbon Nanotubes/Polylactic Acid Composite Fibers. Phys. B Condens. Matter. 2012;407:2451–2457.
    doi: 10.1016/j.physb.2012.03.045google scholar: lookup
  28. Liu H, Wang S, Qi N. Controllable Structure, Properties, and Degradation of the Electrospun PLGA/PLA-Blended Nanofibrous Scaffolds. J. Appl. Polym. Sci. 2012;125:E468–E476.
    doi: 10.1002/app.36757google scholar: lookup
  29. Haroosh HJ, Chaudhary DS, Dong Y. Electrospun PLA/PCL Fibers with Tubular Nanoclay: Morphological and Structural Analysis. J. Appl. Polym. Sci. 2012;124:3930–3939.
    doi: 10.1002/app.35448google scholar: lookup
  30. Liu X, Huang C, Feng Y, Liang J, Fan Y, Gu Z, Zhang X. Reinforcement of a porous collagen scaffold with surface-activated PLA fibers.. J Biomater Sci Polym Ed 2010;21(6-7):963-77.
    doi: 10.1163/156856209X461034pubmed: 20482996google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,359 horse owners like you who receive our email updates on horse health and nutrition.