Dexamethasone Prodrugs as Potent Suppressors of the Immunostimulatory Effects of Lipid Nanoparticle Formulations of Nucleic Acids
This week we profile a recent publication in the Journal of Controlled Release from
Dr. Pieter Cullis, Sam Chen (left) and Josh Zaifman (right) at the UBC Life Sciences Institute.
Can you provide a brief overview of your lab’s current research focus?
The Cullis Lab at UBC has always been interested in developing novel drug delivery technologies that can be applied to a range of therapeutic or diagnostic agents, from small molecules to metallic nanoparticles. We have had a long standing and excellent collaboration with Dr. Marco Ciufolini’s Lab in the Department of Chemistry. In this example, we are exploring chemical modifications to compounds that make them amenable to various nanoparticle delivery systems.
What is the significance of the findings in this publication?
In this publication, using a prodrug approach, we demonstrate the ability to co-deliver different therapeutic agents within a single nanoparticle. Co-delivery has always been very challenging and here, we are able to deliver two classes of drugs (i.e. macromolecules, such as nucleic acids, along with small molecules like corticosteroids). This combination was chosen because nucleic acid therapeutics generally cause an undesired immune stimulation in the patient which is managed by administration of immunosuppressants. By co-delivering the corticosteroid and immune-stimulating therapeutic cargo in a single package, we are able to greatly reduce the unwanted immune response.
What are the next steps for this research?
We continue to explore different combinations of drugs in addition to prodrug design. The use of a corticosteroid prodrug along with nucleic acids in lipid nanoparticles is an example that demonstrates the viability of this approach. One can envision customizing a nanoparticle to deliver a packet of drugs that can act synergistically for a therapeutic effect. The ultimate goal is to enable combination treatments that have positive impacts on patient well-being.
This research was funded by:
Canadian Institutes for Health Research (CIHR) and W. Garfield Weston Foundation