Oral delivery is the most common and convenient method for administering medication due to its low-cost, non-invasive nature, ease of self-administration and increased patient compliance. Traditionally this method is suitable for small molecule drugs, though this is now being explored for emerging biologic therapeutics such as small interfering RNA (siRNA).
siRNA drugs, which can selectively silence disease-causing genes, show promise for treating challenging conditions. However, their rapid degradation in the gastrointestinal (GI) tract and poor systemic absorption make oral delivery difficult.
A series of pre-clinical studies from N4 Pharma has recently shown that Nuvec® can effectively trap and protect the siRNA from enzyme degradation. Nuvec® can be lyophilised to create a powdered form that allows loading of the siRNA/Nuvec® into enteric-protected capsules (and potentially compressed tablets) for targeting to particular GI locations.
At the site of action, the capsule dissolves and the Nuvec® particle enters the target cells where the siRNAs degrade a homologous mRNA sequence in the cell, reducing protein production and inhibiting growth with precise targeting and minimized toxicity, immune response, and side effects.
Recent animal studies demonstrated the successful oral delivery of Nuvec® loaded with a DNA plasmid for ovalbumin using enteric-coated capsules. The capsule’s contents were released in the intestine, taken up by intestinal cells, and successfully transfected, resulting in ovalbumin production. A related study also showed protein/antigen and immunoglobulin (IgG) antibody expression.
N4 Pharma’s oral IBD product, N4 101, is designed to showcase the key benefits of the Nuvec® delivery technology where other approaches struggle, for example:
- Straightforward loading of multiple RNA therapeutics onto the same particle
- Protection of the payload from enzyme degradation to allow oral delivery to the gut
- Functionalisation to target specific cells.