Injectable Crosslinked Hydrogels for Posterior Protein DeliverY
- Provide a rapidly crosslinking, transparent, injectable delivery system
- Are easily manufactured
- Have controlled physical properties, including: gelation time, degradation time, mechanical strength and transparency
- Are zero-swelling
Currently, retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the main causes of vision loss in the aging population. Current therapies typically require frequent injections that can cause considerable patient non-compliance and complications that can put the patient’s vision at risk.
We have developed novel POEGMA-based reactive polymers to provide long-term delivery (months) to the back of the eye.
Description of the Invention
Our polymers rapidly gel in situ, forming hydrogels upon mixing. The hydrogels exhibit tunable structural mechanics and PEG-like protein and cell repellency. The non-cytotoxic poly(oligoethylene glycol methacrylate) (POEGMA) precursors are functionalized with reactive moieties that quickly and reversibly chemically crosslink upon contact in water, under physiological conditions, to form a hydrogel. The system is injectable, eliminating the need of invasive surgical procedures along with the associated discomfort and risk of infection.
In addition to displaying all the favorable biological properties of poly(ethylene glycol) hydrogels, our materials promote:
- Reduced protein adsorption,
- Reduced cell adhesion
- The facile incorporation of non-toxic moieties in vitro and in vivo, into the precursors.
The physiochemical properties of these materials have been successfully tuned for the controlled release of proteins (BSA, IgG and fibrinogen), as well as to form highly optically transparent gels. In all POEGMA hydrogel formulations, in vitro studies and in vivo studies following subcutaneous injections in Balb/c mice, show high viability and good tolerability. POEGMA hydrogels offer an easily manufactured, modifiable, injectable alternative to PEG hydrogels. Protein release rates of at least 14 μg protein per week for up to two months using model proteins (BSA, Fib, IgG). We are currently working to optimize protein release profiles.
Potential Uses and Applications
Our in vivo reversible-fast-crosslinking hydrogels have the unique ability to deliver high molecular weight protein-based pharmaceuticals, via a transparent, zero-swelling gel, thus exhibiting exceptional potential for use in the treatment of retinal diseases. Our materials have also shown considerable promise in biomaterial coatings, as a subcutaneous protein release device and a potential material for wound dressings or medical adhesives.