Abstract
Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to the market. However, applications of such systems are limited due to inefficiency, cytotoxicity and/or immunogenicity. At the same time, the field of natural drug carrier systems has grown rapidly. One of the most prominent examples of such natural carriers are extracellular vesicles (EVs). EVs are cell-derived membranous particles which play important roles in intercellular communication. EVs possess a number of characteristics that qualify them as promising vehicles for drug delivery. In order to take advantage of these attributes, an in-depth understanding of why EVs are such unique carrier systems and how we can exploit their qualities is pivotal. Here, we review unique EV features that are relevant for drug delivery and highlight emerging strategies to make use of those features for drug loading and targeted delivery.
Highlights
Extracellular vesiclesExtracellular vesicles are phospholipid bilayer-enclosed vesicles secreted from all cell types and can be found in tissue culture supernatants as well as biological fluids such as blood, saliva, breast milk, cerebrospinal fluids and malignant ascites [15,16,17]
Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to the market
A collection of proteins have been confirmed to be enriched in extracellular vesicles (EVs), including both cytosolic and membrane proteins, e.g. annexin II and heat shock proteins, MHC class II complexes, integrins and tetraspanins, in addition to ALG-2-interacting protein X (Alix), tumour susceptibility gene 101 (TSG101), as well as cell-specific proteins that may have an influence on EV function [23]
Summary
Extracellular vesicles are phospholipid bilayer-enclosed vesicles secreted from all cell types and can be found in tissue culture supernatants as well as biological fluids such as blood, saliva, breast milk, cerebrospinal fluids and malignant ascites [15,16,17]. Other studies show that EVs have similar clearance kinetics as liposomes [28], or that they are even cleared more rapidly following intravenous injection [29,30] These seemingly contradictory results may be a consequence of differences in EV cell source, isolation procedure (known to affect EV integrity and biophysical properties [31,32]), or specific EV protein/lipid surface profile, the underlying mechanisms remain to be elucidated. Studies have shown that specific progenitor cell derived EVs convey biological cargo that promotes angiogenesis and tissue repair and modulates immune functions [37] As such, these EVs exhibit a promising source of acellular therapy for various conditions, which can be taken advantage of by further engineering these EVs for the delivery of therapeutics. Importance to first understand (1) why EVs may be suitable drug delivery vehicles and what their potential benefits are over synthetic vehicles, and (2) how EVs can be engineered and pharmaceutically developed in such a way that clinical usage of EVs as drug carriers may become a reality
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