Delivery of Small Interfering RNA and Micro RNA Through Membrane-Disruptive, Responsive Nanoscale Hydrogels
Life Sciences : Drug Delivery
Available for licensing
- Nicholas Peppas, Sc.D. , Biomedical Engineering
- William Liechty , University of Texas at Austin
Nearly all delivery systems undergoing clinical trials (although no RNAi therapeutic has achieved FDA approval) rely on naked siRNA, conjugated polymers, or lipid carriers for topical and intravenous administration and do not possess attributes that render them useful delivery vectors for GI targets. A common issue that plagues delivery of agents for RNA interference is the need for safe, effective delivery vectors capable of transporting therapeutic cargoes to their subcellular site of action. The market for RNAi therapeutics will be an estimated $4 billion by 2017, provided the delivery challenges can be ameliorated. This invention meets these criteria and is specifically engineering to function in a physiological environment where contemporary technologies are not well-suited.
Researchers at The University of Texas at Austin have prepared nanoscale, pH responsive polycationic networks containing ionizable amine groups engineered for delivery of anionic biological therapeutics, including DNA, small interfering RNA, and microRNA. These networks are highly effective at binding RNA, enhancing cellular internalization, mediating endosomal release, and subsequently inducing gene knockdown. These networks are synthesized using a rapid and scalable photoemulsion polymerization. Physicochemical properties of nanoscale hydrogel networks, including volume swelling ratio, critical swelling pH, membrane-disruptive ability, and cytocompatibility can be modulated by tuning polymer composition. These tunable properties endow the polymer networks with an excellent combination of properties for intracellular drug delivery—highly efficient membrane destabilization and low cytotoxicity.
- Rapid synthesis using facile and well-understood polymerization mechanisms
- Tunable copolymer composition and physicochemical properties
- High degree of siRNA loading (up to 33 wt%)
- Rapidly degradable (under 10 minutes) network structure
This invention has been specifically designed for delivery to disease sites along the gastrointestinal tract, with potential utility in Crohn´s disease, ulcerative colitis, celiac disease, and gastrointestinal carcinomas.
Proof of concept