Enhanced Delivery of Viral Vectors to Striatum with Solid-State Biodegradable Matrices
Rapid Response Innovation Awards, 2009
When treating patients with neurological disorders, physicians frequently administer drugs through a small plastic tube or needle placed into the target area of the brain. Unfortunately, the delivered drug frequently seeps back along the insertion track. As a result of this “back leak”, more of the drug must be injected into the brain and the drug comes into contact with normal brain tissue where it may have harmful effects. The aim of these studies is to develop technology that allows more of the delivered drug to remain in the target area.
The proposed experiments aim to reduce back leak of drugs when they are injected into brain tissue. To accomplish this, we will use compounds called hydrogels, which are liquid at room temperature but become solid when warmed to body temperature. We will exploit this characteristic of hydrogels by injecting indicator virus/hydrogel solutions into the brain and then localizing the solidified material. Our hypothesis is that the solidified hydrogel will lead to better retention in the target site with reduced back leak. We will target striatum and compare delivery and retention between two different hydrogels and more conventional fluid based delivery systems. As endpoints, we will measure diffusion out of the target area and back leak along the needle track.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If successful, these experiments will lead to better delivery of therapeutic molecules to the striatum of patients with Parkinson’s disease. With this delivery technique, retention in the striatum will be improved and there will be less back leak along the needle tract. Both of these should lead to better efficacy with reduced side effects.
These experiments will provide a proof-of-concept to determine if hydrogels improve delivery to striatum. If our hypothesis is correct, these hydrogels will lead to better delivery and retention of our indicator viruses. We would then move to studies investigating enhanced efficacy of therapeutic agents with hydrogels in animal models of Parkinson’s disease.
The goal of our research is to increase the effectiveness of drug delivery to the brains of patients with Parkinson’s disease. Specifically, our work addresses the problem that when drugs are injected into the brain, a measurable amount leaks back through the injection site. This back-leak is potentially harmful because it increases the possibility of toxic side effects. We hypothesized that if one could deliver the drugs in a material that transforms into a gel once injected into brain, back-leak might be eliminated. Compounds are available (called hydrogels) that are liquid at room temperature and become a gel when warmed to body temperature. While hydrogels have been used successfully in solid tumors, they have not been used in the brain. Our first experiments, therefore, were to determine if hydrogels could be used safely in the brain. We have completed experiments showing that they are safe to use in the brain. Our data show that the hydrogels did not cause infection or damage in the brain. In our next phase, we will test whether or not hydrogels reduce back-leak.
Associate Professor at Mt. Sinai School of Medicine
Location: New York, New York, United States