Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives

Abstract

Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes. In this current review, we summarize the most up-to-date knowledge about the complex biological journey of exosomes from biogenesis and secretion, isolation techniques, characterization, loading methods, pharmaceutical and therapeutic applications, challenges and future perspectives of exosomes.

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

“…EV post-loading is achievable via physical and chemical modifications, which are the two major ways for transfering the cargo of interest to EVs. Incubating EVs with the cargo of interest (passive loading) is a convenient and effective way, which was applied to load EVs with nucleic acids, proteins or peptides, drugs, and nano-materials ( 205 , 290 , 291 ). Different methods are proposed for direct loading of EVs with cargos of interest, such as the application of transfection reagents, electroporation, incubation, sonication, freeze/thaw cycles, saponin, extrusion and dialysis ( 205 , 270 ).…”

Extracellular Vesicles for Therapeutic Nucleic Acid Delivery: Loading Strategies and Challenges

“…These nanosized carriers transfer various cargoes into the body, protecting them from enzymatic degradation. The unique architecture and content of EVs have stimulated research aimed at their use as drug carriers, diagnostic markers, immunotherapeutic agents, and for regenerative medicine [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Two general pathways of EV formation have been described to date: via the intracellular endosomal compartments and via the separation of vesicles from the plasma membrane [ 52 ].…”

Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications

“…First, the extraction and isolation of exosomes can be more inefficient due to the complexity of the technology. Low yields and high costs prevent exosomes from being used as drug delivery vehicles on a large scale ( 107 , 108 ). Second, exosomes are limited in their drug loading.…”

“…Exosomes have a high degree of heterogeneity, increasing their quality control challenge. The lack of knowledge about exosome properties and physiopathology makes it difficult to assess drug delivery efficacy ( 23 , 107 ). Therefore, significant efforts addressing these challenges are necessary to facilitate the clinical application of exosome-based drug delivery systems.…”