Nanoparticle intraocular drug delivery system
Age-related Macular Degeneration (AMD) affects millions of people, progressively robbing them of their central vision and significantly reducing their quality of life. Without central vision, they are unable to read, recognize faces, drive, or perform countless daily activities. The vast majority of AMD cases consist of the “dry” form of the disease, in which the retinal pigment epithelium (RPE) atrophies, leading to the loss of the associated photoreceptor cells. There are no currently approved treatments to halt or reverse the loss of vision once dry AMD is recognized.
The Technology Solution
Researchers in the Department of Ophthalmology at the University of Tennessee Health Science Center have demonstrated that certain glycans support outer segment assembly and promote photoreceptor cell survival, even in the complete absence of an RPE. In addition, the researchers have developed nanoparticles for delivery of the glycan to the posterior segment of the eye via an intraocular injection composed of the nanoparticle and the glycan. The nanoparticles are generated from poly ortho ester (POE). While POEs have been evaluated as a bolus drug delivery system and have minimal to no toxic effects [Einmahl, 2002 ], the inventors are the first to use this polymer to generate nanoparticles for use as an intraocular delivery system. The researchers have designed the nanoparticles such that the nanoparticles can be used for both hydrophilic and hydrophobic drugs. The nanoparticles degrade at slow rate and exhibit slow, long-term drug release with little to no cytotoxic side effects. Preliminary results also indicate that the nanoparticles are not taken up by the cells, a desired characteristic of such a delivery system. Preliminary in vivo studies show that the nanoparticles do not enter the retina but remain in the vitreous region of the eyes, where it can provide long term drug release. The studies conducted thus far have been with other model drugs, but the novel formulation of the nanoparticle and the glycan is expected to provide long-term release of the glycan to provide effective treatment of AMD. The nanoparticle delivery system was able to provide drug delivery for at least 14 weeks, with initial data indicating possible delivery up to 107 weeks. This is in vast contrast to some currently marketed ophthalmic drugs requiring weekly and monthly drug injections for treatment. In addition, the nanoparticle is being designed such that it can accommodate other drugs for delivery to other tissues within the body.
Advantages and Benefits
• Non-toxic, biocompatible, biodegradable delivery system
• Long-term zero order release; No initial lag time in release and degradation
• Eliminates need for multiple repeated injections, minimizing the risks to patients
• Easy handling
• Provides good drug availability
• Safe and effective delivery via the vitreal chamber
• US Provisional Patent Application No. 61/599075, filed February 2012
• US Nonprovisional Patent Application No. 13/767734; filed February 2013
Dr. Monica Jablonski is a Professor of Ophthalmology at the University of Tennessee Health Science Center. Her research interests are mechanisms that regulate photoreceptor outer segment assembly, mouse models of eye disease, proteomics, retinal cell biology, and mutagenesis.