Drug Delivery Systems

Exosomes have great potential as drug delivery vehicles through the loading of therapeutic agents into, within, or on the lipid bilayer membrane. Exosomes can be derived from a wide variety of sources (plasma, milk, plants, cancer cells, stem cells, etc.) and loaded by numerous methods (incubation, electroporation, sonication, freeze-thaw, extrusion, etc.) with clinically approved drugs or novel drug classes (mRNA, siRNA, miRNA, proteins, etc.). Exosomes as delivery vehicles effectively function as nanoparticle carriers similar to existing lipid nanoparticle-based drugs (Doxil or Moderna Covid-19 vaccine)—they are essentially the naturally occurring version of synthetically manufactured liposomes/lipid-based nanoparticles. Exosomes have many advantages over liposomes including: being derived from endogenous cellular processes, less toxicities due to natural cellular lipids, higher in-vivo stability, better biodistribution patterns without being cleared by the liver and reticuloendothelial system, and higher drug delivery efficiency. Additionally, exosomes can be functionalized with targeting capabilities by adding proteins, peptides, or antibodies to the surface of the exosomes. This will allow for the exosomes to specifically deliver the loaded drug to the cell types of interest, and not to healthy or unintended cell types. For example, targeted delivery of chemotherapeutic agents would allow for a lower total drug dose, which would reduce patient exposure to toxic agents and thus reduce side effects without compromising drug efficacy.

 

Using exosomes to load and deliver drugs has already been shown to be effective. Doxorubicin and paclitaxel are the two most common drugs used in pre-clinical experimentation models, and both of these drugs have been successfully loaded into exosomes from numerous sources including monocyte, breast and ovarian cancer cell, mesenchymal stem cell, macrophage, and bovine milk derived exosomes. In-vitro and animal studies have shown positive results compared to the free drug and even the FDA approved liposomal Doxorubicin (Doxil) in that the outcomes of these trials have enhanced suppression of tumor growth, reduced systemic side effects, and passage of biological barriers including the blood-brain-barrier. Further, nanoparticle encapsulation of a drug can improve drug solubility, stability, and half-life, all of which prove challenging for BCS Class II and IV drugs. 

 

Novel drugs like mRNA, siRNA, miRNA, and proteins have also shown therapeutic properties in a wide variety of disease states. It is absolutely required to encapsulate nucleic acid or protein-based drugs inside of a vesicle to protect them from degradation by proteases and endo/exonucleases. This class of biologic drugs have been successfully loaded into exosomes derived from a wide variety of sources. Exosomes have proven to be a gamechanger in the field of targeted drug delivery through their ability to carry a wide variety of cargo, protect that cargo from degradation, and specifically deliver that cargo to the cell types of interest.