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

Int J Mol Sci. 2023 Mar 17;24(6):5735. doi: 10.3390/ijms24065735.

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.

Keywords: cyclosporin A; immune-mediated keratitis; poly (L-lactide-co-DL-lactide); thermoplastic polyurethane.

MeSH terms

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

Substances

  • Cyclosporine
  • Polyurethanes