In Situ Gelling of Degradable Polymers for Drug Delivery to the Back of the Eye
Novel polymer drug depot:
- Forms transparent, non-shrinking gel in situ, following injection as liquid
- Provides sustained drug release for months
- Reveals no evidence of toxicity in rats, following a 2-week intravitreal exposure
The retinal disease segment of the global ophthalmic market is expected to reach $7.7-billion USD by 2016; however, there is still a significant need for improved drug delivery systems to deliver therapeutics to the back of the eye. Current therapies typically require frequent injections that cause considerable discomfort and are associated with complications that put the patient’s vision health at risk.
We have developed optically transparent, in situ gelling, non-shrinking, degradable polymers to provide long-term delivery (over three months) of a wide range of bioactive agents (including proteins, cells, genes and both hydrophilic and hydrophobic compounds) to the back of the eye to treat posterior eye conditions.
Description of the Invention
Our family of in situ gelling drug delivery copolymers based on poly(N-isopropylacrylamide) (PNIPAAm) can be injected as a liquid, drug-infused polymer suspension into the posterior segment of they eye. The polymer rapidly transforms from liquid to gel, creating a solid drug reservoir directly within the vitreous cavity without the use of invasive surgical techniques. The optically transparent non-shrinking polymers provide sustained release of low levels of pharmaceutical and are degradable, leaving the body via natural clearance mechanisms without invasive surgical intervention. Rigorous intraocular compatibility testing demonstrated exemplary results, revealing no changes in retinal function as measured via electroretinography (ERG) following intravitreal injection of a 5 wt% polymer suspension into the vitreous of Sprague Dawley rats. Extensive in vivo imaging verified the RPE monolayer and retinal vasculature remained healthy, intact and normal following a two-week intravitreal exposure to the polymer.
Potential Use and Applications
Our novel polymers can potentially deliver a wide range of bioactive agents to the back of the eye to treat posterior eye conditions. The novel polymers could also be used as a vitreous substitute or in conjunction with a semi scleral lens for front of the eye delivery.