Small or large we deliver all! It's all about DELIVERY - Kumar Lab

Many drugs must overcome biological barriers and find their way to diseased tissues to be therapeutically effective.

This can be achieved by encapsulating drugs into biodegradable nanoparticle ‘transporters’ decorated with molecules called ‘ligands’ that bind to specific receptors on the cell surface.

However, the body’s own ligands can out-compete those on the transporters if they are not designed for efficient receptor binding.

We have used a natural ligand called gambogic acid that avoids competition from the body’s own ligand called transferrin when binding to the target ‘CD71’ cell surface transferrin receptor.

Crucially, we discovered that the gambogic acid ligands need to be spaced at regular intervals and densities across the nanoparticle surface to maximize transport. This was only possible with our chemically engineered nanoparticle transporters.

The therapeutic potential of our technology has been demonstrated in models of disease. For example, systemic lupus erythematosus is an autoimmune disease that can cause swollen lymph nodes and is currently treated with systemic disease modifying agents.

By targeting our transporters to the lymph nodes after their absorption from the gut, we increased the bioavailability of cyclosporin four-to-eighteen-fold, potentially improving its therapeutic efficacy.

We have shown similar data for cisplatin-induced acute kidney injury model, for which there is no FDA-approved treatment. Encapsulating a potential drug called urolithin A into our gambogic acid-decorated nanoparticles enhanced its peroral uptake seven-fold, reducing mortality by almost two-thirds.

Our customizable drug-transporters clearly overcome biological barriers such as the small intestine. We intend to use this breakthrough technology to minimize drug attrition rates in the pharmaceutical industry or offer a route to repurposing existing drugs for diseases that currently lack effective treatments.