The Department of Veterans Affairs is offering to businesses a novel medical technology for the development of new products.
Targeting drugs to the site of inflammation has remained a challenge in inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) because of the lack of vehicles that can carry sufficient therapeutic cargo or that can release the drugs they carry at the site of inflammation. It is challenging to deliver drugs to the gastrointestinal tract, particularly the colon, due to degradation by digestive enzymes. Various carriers have been designed to release the drug at a specific pH value, to be resistant to digestive enzymes, and/or to require bacterial cleavage for activation, and several of these types of carriers are currently being investigated. However, most delivery systems under development still require the initial incorporation or administration of drugs in large doses, multiple times a day, resulting in poor patient compliance and significant side effects.
To address this issue of delivery, VA funded researchers have developed biodegradable nanoparticle (NP) vehicles that have little or no associated toxicity. The vehicle is assembled such that a targeting agent (such as an antibody or fragment, ligand, receptor, chemoattractant agent, extracellular matrix protein) is associated with the NP, thereby forming a core structure, The core is encapsulated in a hydrogel.
These vehicles can be used to target TNFα with siRNAs for the treatment of bowel diseases such as colitis and colon cancer. With the targeting agent improving the kinetics of endocytosis as well as the ability of the NP to target a given cell (such as a macrophage or cancer cell) the NPs can enter cellular targets by endocytosis. The resulting endosome is degraded, allowing the release of the double-stranded RNAs delivered by the constructs and their incorporation into the RNA-induced silencing complex (RISC).
Targeting is the selective delivery of an agent to an identified cellular or molecular entity to the substantial exclusion of others. With this technology, the delivery vehicles can target colonic macrophages or dendritic cells by selectively delivering a therapeutic or diagnostic moiety to those cells, to the substantial exclusion of others. Among the other advantages of the NP delivery vehicles is an ability to directly release specific siRNAs to target cells. The NPs are readily able to pass through physiological barriers and evade phagocytosis. They also can show rapid mixing kinetics, accept high loading concentrations, confer little or no toxicity, and resist degradation.
- Versatile delivery system for therapeutic and diagnostic agents that can overcome physiological barriers and target inflamed or cancerous regions of the colon
- Constructs can be formulated for oral administration, are well tolerated, and offer advantages with regard to patient compliance
- Allows for the administration of less of a given therapeutic or diagnostic agent (than would be required without the delivery vehicle) to achieve similar therapeutic efficacy or diagnostic success
- Businesses can acquire the technology and productize by licensing US patent 9,717,695, and multiple international patents pending, from the VA
- Potential for collaboration with VA researchers to further develop this technology
- TechLink navigates businesses through licensing at no charge