Novel functionalization of liposomic nano-vehicles for strongly-enhanced drug delivery

Introduction

Delivery to diseased cells or tissues of therapeutic agents attached or encapsulated in nanoparticles – nanomedicine – presents many benefits and comprises a rapidly-growing multi-billion-euro market.

Lipid-based Drug Delivery

Lipid-based drug-delivery nano-vehicles, where drugs (not least the recent, very widely used, mRNA-based COVID-19 vaccines) are encapsulated in lipid vesicles (liposomes) or lipid nanoparticles, form a substantial part of that market. Nearly all FDA-approved liposomal vehicles are functionalized with poly(ethylene glycol), PEG, moieties, the current gold standard.

Benefits of PEGylation

These PEG moieties act to:

• Sterically stabilize the vesicles
• Increase their blood-retention time
• Enhance their therapeutic efficiency

Drawbacks of PEGylation

At the same time, such PEGylation has several drawbacks, including:

1. Reduced cellular uptake
2. Accumulation of PEG in tissues
3. Accelerated blood clearance on repeated intravenous dosage due to heightened immune response

Novel Functionalization Approaches

We use novel functionalization approaches to overcome these drawbacks. The present project explores the innovation dimension of our new approach.

Key Questions

In particular, we seek to answer:

• Is it effective?
• Is it efficient?
• How widely applicable is it?
• What is the IPR position for future exploitation of this new strategy?

These questions illustrate the high-risk/high-gain nature of this proposal and are addressed here through several inter-related work packages.

Project Impact

Success of our project in demonstrating that our novel approach is significantly superior to the currently universally used PEGylation would not only have a therapeutic advantage for many diseases but also tap into a large and growing market.