Researchers at Pitt are exploring a novel approach to the treatment of inflammatory eye diseases, particularly dry eye disease (DED), using a controlled drug delivery system. The key focus is on utilizing histone deacetylase inhibitors (HDACi) to modulate the ocular immune environment and induce the differentiation and expansion of regulatory T cells (Tregs).
Description
The PLGA polymer particles encapsulating the HDACi can range in size from nanoparticles to microparticles, providing a long-term ophthalmic drug delivery system. By using HDACi to induce Tregs, the invention has the potential to provide long-term benefits without the side effects associated with prolonged use of corticosteroids, such as glaucoma and retinopathy. The researchers developed a controlled delivery system to locally release SAHA and present preliminary data suggesting its potential to prevent ocular tissue damage, enhance FoxP3 expression (a Treg marker), and reduce the pro-inflammatory environment in DED.
Applications
- Dry eye disease treatment
- Inflammatory eye disease treatment
Advantages
This is a novel controlled release drug delivery system. This invention utilizes components such as HDACi, like SAHA (Suberoylanilide Hydroxamic Acid), and biodegradable poly(lactic-co-glycolic acid) (PLGA) polymer particles. The current standard of care for DED, which includes artificial tears, punctal plugs, and anti-inflammatory treatments like corticosteroids, only addresses the symptoms of the disease and not the underlying pathology. In contrast, this invention aims to restore the homeostatic balance in the ocular tissue by re-establishing the immunological balance, rather than solely targeting a specific pathogenic cell.
Invention Readiness
This technology is at the level of in vivo data. The researchers fabricated SAHA-loaded microspheres using a single-emulsion evaporation technique and evaluated their efficacy in a ConA-induced murine model of DED. The administration of SAHA microspheres prevented the loss of tear production, reduced corneal fluorescein staining, and preserved goblet cell density compared to control groups. The SAHA microspheres significantly reduced the mRNA expression of pro-inflammatory cytokines IL-12, IFN-γ, and IL-6, while increasing the expression of the Treg marker FoxP3. The SAHA microspheres were able to shift the ocular immune environment towards an anti-inflammatory state by enhancing Treg function and suppressing effector T cell-mediated inflammation.
IP Status
https://patents.google.com/patent/US11844862B2
