John Garner

mPEG-PLGA from PolySciTech used in development of microparticle-based delivery system for regulatory T-cell induction factors as an anti-inflammatory therapy

Blog Post created by John Garner on Dec 19, 2017


Ratay, 2017 anti-inflammatory treg mPEG-PLGA.JPG

Several diseases and conditions are associated with an excessive immune response which leads to inflammation that can damage tissue. There are medicines available which can reduce the immune response (e.g. anti-histamines, steroidal anti-inflammatories) however, these all have side-effects due to their relatively non-specific nature in globally preventing immune response. The immune system itself has a built-in regulatory mechanism which acts through regulatory T-cells that act to reduce immune response and improve the recognition of antigens as ‘self.’ A more effective and therapeutic strategy is to provide factors which promote the formation and recruitment of regulatory t-cells to a site of inflammation. Recently, researchers at The University of Pittsburgh used mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to create a microparticle designed to release pro-regulatory-t-cell factors into the eye as a means to reduce localized inflammation by promoting the body’s own feedback system to control the immune response. This research holds promise not only to treat ocular diseases, but to be applied to other disease in which excessive immune response is implicated. Read more:  Ratay, Michelle L., Stephen C. Balmert, Abhinav P. Acharya, Ashlee C. Greene, Thiagarajan Meyyappan, and Steven R. Little. "TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model." Scientific Reports 7, no. 1 (2017): 17527. https://www.nature.com/articles/s41598-017-17869-y

 

  “Abstract: Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body’s own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.”

Outcomes