Wednesday, March 22, 2023

PLGA-PEG-PLGA from PolySciTech used in development of thermogel for treatment of corneal injuries.


Even relatively minor ocular injuries can lead to downstream blindness due to localized inflammation and overgrowth of blood vessels occurring in response to the injury. This result can be prevented by TNF and VEGF inhibitors however this requires consistent application of the drugs during the healing process. Researchers at Harvard Medical School, Massachusetts Eye and Ear Infirmary, and University of New Mexico School of Medicine utilized PLGA-PEG-PLGA (AK141) from PolySciTech division of Akina, Inc. ( to develop a thermogel for long-acting delivery of adalimumab and aflibercept for ocular injection. This research holds promise to reduce the incidence of blindness by offering a new option for treatment of ocular damage. Read more: Zhou, Chengxin, Fengyang Lei, Pui-Chuen Hui, Natalie Wolkow, Claes Dohlman, Demetrios G. Vavvas, James Chodosh, and Eleftherios I. Paschalis. "A novel sustained release therapy of combined VEGF and TNF-α inhibitors leads to pan-ocular protection for months after severe ocular trauma." bioRxiv (2023): 2023-03.

“Purpose: To develop a clinically feasible and practical therapy for multi-ocular protection following ocular injury by using a thermosensitive drug delivery system (DDS) for sustained delivery of TNF-alpha and VEGF inhibitors to the eye. Methods: A thermosensitive, biodegradable hydrogel DDS (PLGA-PEG-PLGA triblock polymer) loaded with 0.7mg of adalimumab and 1.4 mg of aflibercept was injected subconjunctivally in Dutch-belted pigmented rabbits after corneal alkali injury. The polymer was tuned to transition from liquid to gel upon contact with body temperature without need of a catalyst. Control rabbits received 2mg of IgG loaded DDS or 1.4mg aflibercept loaded DDS. Animals were followed for 3 months and assessed for tolerability and prevention of corneal neovascularization (NV), improvement of corneal re-epithelialization, inhibition of retinal ganglion cell (RGC) and optic nerve axon loss, and inhibition of immune cell infiltration into the cornea. Drug release kinetics was assessed in vivo using aqueous humor protein analysis. Results: A single subconjunctival administration of dual anti-TNF-alpha/anti-VEGF DDS achieved sustained 3-month delivery of antibodies to the anterior chamber, iris, ciliary body, and retina. Administration after corneal alkali burn suppressed CD45+ immune cell infiltration into the cornea, completely inhibited cornea NV for 3 months, accelerated corneal re-epithelialization and wound healing, and prevented RGC and optic nerve axon loss at 3 months. In contrast, anti-VEGF alone or IgG DDS treatment led to persistent corneal epithelial defect, increased infiltration of CD45+ immune cells into the cornea, and significant loss of RGCs and optic nerve axons at 3 months. Aqueous humor protein analysis showed first-order release kinetics without adverse effects at the injection site. Conclusion: Sustained concomitant inhibition of TNF-alpha and VEGF using a biodegradable, slow-release thermosensitive DDS provides significant ocular protection and prevents corneal neovascularization and irreversible damage to retina and optic nerve after corneal alkali injury. This therapeutic approach has the potential to dramatically improve the outcomes of severe ocular injuries in patients.”


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