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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.
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Publication Date: 2023-03-17 PubMed ID: 36982806PubMed Central: PMC10057311DOI: 10.3390/ijms24065735Google Scholar: Lookup
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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.

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