Once thought of as cellular "garbage bags," extracellular vesicles (EVs) are now understood to play critical roles in cell-to-cell communication within an organism. EVs such as exosomes and liposomes have been studied intensively and, due to the protective effects these lipid envelopes have on their molecular contents, have become models for improved vaccine and drug delivery systems.
The efficacy of EVs for tissue- and cell-specific localization of contained drug compounds can be further enhanced by coating them with certain polymeric substances. In particular, the presence of the hydrophilic polymer polyethylene glycol (PEG) on "PEGylated" liposomal surfaces has been shown to confer several benefits:
- Creating a hydrophilic barrier to reduce immune system interaction
- Rendering the liposomal carrier "immune-evasive" by hindering antibody binding
- Shielding the carrier's surface-expressed immunoglobulins and complement proteins, avoiding tagging for uptake (opsonization) and elimination by the body’s mononuclear phagocyte system (MPS)
- Increasing liposomal carrier circulation times, allowing the vesicle to reach intended target cells
While PEG-coated "stealth" liposomes have improved drug delivery, more recent research has also revealed a few issues, including:
- PEG degradation under mechanical stress
- Immunogenicity of PEG itself in certain individuals
- Pharmacokinetic changes due to the addition of PEG
- Possible PEG accumulation in the body
Currently, research continues into potential alternative polymeric coatings that might retain all the benefits with fewer drawbacks.
Immordino, Maria Laura, et al. Stealth Liposomes: Review of the Basic Science, Rationale, and Clinical Applications, Existing and Potential. National Library of Medicine, National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/.
Jhan, Yong-Yu, et al. Polymer-Coated Extracellular Vesicles for Selective Codelivery of Chemotherapeutics and siRNA to Cancer Cells. Figshare. https://figshare.com/
Kooijmans, S A A, et al. Pegylated and Targeted Extracellular Vesicles Display Enhanced Cell Specificity and Circulation Time. National Library of Medicine, National Center for Biotechnology Information. https://pubmed.ncbi.nlm.nih.gov/.
Walker, Sierra, et al. Extracellular Vesicle-Based Drug Delivery Systems for Cancer Treatment. National Library of Medicine, National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/.