Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments

Abstract

Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.

Therapeutic miRNA-Enriched Extracellular Vesicles: Current Approaches and Future Prospects

“…However, to overcome the limitation of insufficient production of natural EVs, extrusion of cells through a series of ultrafiltration lead to the production of extracellular vesicle mimetics (EVMs). It is worth noticing that the same number of cells can provide 20–100 fold more EVM than natural EVs [ 78 ]. In addition to human cell-derived EVs, EVs can be obtained from plants, referred to as plant-derived EVs [ 79 ].…”

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

“…Though several techniques are in use for drug loading and targeted delivery, a standard effective method is still lacking. Existing methodologies include the incubation of drugs with EVs, electroporation or saponification to induce the formation of small pores within the membranes, freeze-thaw methods that can cause the degradation of many EV proteins, and the transfection of nucleic acids into the secreting cells, among others 229 . Any method can be selected depending on the study demand and its advantages.…”

Defining a Regulatory Strategy for ATMP/Aerosol Delivery Device Combinations in the Treatment of Respiratory Disease

“…There has been great interest in EVs from researchers owing to their potential to be used as drug delivery systems, enhancing the target delivery of drugs and surpassing standard drug delivery methods [ 38 ]. The advantages of using EV alternative drug delivery systems have been demonstrated in preclinical models, which have shown a low toxicity; high target efficiency; and the ability to escape degradation, resulting in a slower clearance from the body [ 39 , 40 ].…”

“…EVs obtained from cells are classified based on their size and source; exosomes are a type of EV, along with micro vesicles and apoptotic bodies, that are 30–100 nm in diameter and are not only secreted by MSCs but also by other stem cells, such as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESC), hematopoietic stem cells (HSC), and neural stem cells (NSC) [ 39 , 41 ]. Though these types of stem cells are considered to be safe to use as therapeutics, there are some biosafety concerns associated with their application, such as immune-rejection, tumorigenicity, and the potential for abnormal differentiation [ 42 ].…”