Gelatin Nanoparticle Formulation of TAK1 Inhibitor 5Z-7-Oxozeaenol to Treat Corneal Neovascularization

Article: High-tech eye drop research targets corneal damage
Source: Centre for Eye Research Australia (Australia)
Published: January 25, 2022

Gelatin-nanoparticle-encapsulated 5Z-7-oxozeaenol (lower right)
was significantly more effective at reducing neovascularization
compared to either GNPs or Oxo alone or to saline control

Corneal neovascularization is a complication of many ocular diseases, leading to scarring that permanently impairs corneal transparency. As an alternative to steroids and anti-vascular endothelial growth factor (anti-VEGF) therapies, researchers in Australia are exploring a nanoparticle formulation of a selective inhibitor of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) as a therapeutic option for pathological angiogenesis. In particular, they developed an gelatin-nanoparticles-encapsulated eyedrop formulation of the TAK1 inhibitor 5Z-7-oxozeaenol. Testing the eyedrops on a mouse model showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis further revealed 5Z-7-oxozeaenol mechanism of action through suppressing the cell cycle and DNA replication. The researchers also found that 5Z-7-oxozeaenol reduced angiogenic and cytokine-mediated inflammatory signalling through inhibiting tumor necrosis factor alpha (TNFα)-mediated nuclear factor kappa B (NFκB) signalling. Finally, they showed that a gelatin nanoparticle formulation of 5Z-7-oxozeaenol was significantly more effective compared to free 5Z-7-oxozeaenol in a mouse model of corneal neovascularization with administration frequency as little as once daily, likely due to the longer retention of the gelatin nanoparticles. The research team note the potential of anti-angiogenic therapies not only to treat corneal disease but also to promote the health of a compromised cornea prior to transplant to increase the probability of transplant success. They also hypothesis that a nanoparticle formulation could better penetrate the ocular surface for treatment of more interior eye structures and look to further pre-clinical studies before clinical trials.

My rating of this study: ⭐⭐⭐

Wang JH, Tseng CL, Lin FL, et al. "Topical application of TAK1 inhibitor encapsulated by gelatin particle alleviates corneal neovascularization." Theranostics. 12(2):657-674. 2022. https://doi.org/10.7150/thno.65098