Current state-of-the-art drug carrier systems deliver new ‘biological drugs’ (like proteins and nucleic acids) poorly to the target site. This is something I daily experience in my research on delivery of small interfering RNA. The in vivo challenges are threefold:
• Biological drugs are fragile molecules (subject to degradation and denaturation)
• They need to gain access to the target site
• They need delivery to a specific cell type and even to a specific subcellular location to be active.
Recent research points out an endogenous communication system transporting proteins and nucleic acids between cells, outperforming current synthetic drug delivery systems. These carriers, known as microvesicles, appear Nature’s choice for delivery of biologicals and have created excitement in the research community. Microvesicles encompass a variety of submicron vesicular structures that include exosomes, shedding vesicles, and microparticles. The lipids, proteins, mRNA and microRNA delivered by these microvesicles change the phenotype of the receiving cells. Microvesicles appear to play an important role in many disease processes, most notably inflammation and cancer, where their efficient functional delivery of biological cargo contributes to the disease progress. Up to now, most research addresses the role of microvesicles in cell biology. At the same time, surprisingly little is known about their in vivo kinetics, targeting behavior and tissue distribution from a drug carrier standpoint.
The aim of my proposal is to design and develop microvesicle-inspired drug delivery systems to improve targeting and delivery of biological drugs.
The work plan is divided into two approaches:
1-A synthetic approach based on liposomes or isolated microvesicle constituents
2-A biological approach based on biotechnologically-engineered and cell-produced microvesicles.
The results of this research are expected to improve insights into in vivo behavior of microvesicles and the critical molecules that trigger their delivery and targeting success. It should also be clear which of the two approaches is best suited for the production of pharmaceutically acceptable microvesicle-mimics. Finally, the research should result in a prototype microvesicle-inspired carrier. These results can form the basis for an attractive new generation of microvesicle mimicking drug delivery systems.
Fields of science
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