Exosomes as Naturally Occurring Vehicles for Delivery of Biopharmaceuticals: Insights from Drug Delivery to Clinical Perspectives

Abstract

Exosomes as nanosized vesicles are emerging as drug delivery systems for therapeutics owing to their natural origin, their ability to mediate intercellular communication, and their potential to encapsulate various biological molecules such as proteins and nucleic acids within the lipid bilayer membrane or in the lumen. Exosomes contain endogenous components (proteins, lipids, RNA) that could be used to deliver cargoes to target cells, offering an opportunity to diagnose and treat various diseases. Owing to their ability to travel safely in extracellular fluid and to transport cargoes to target cells with high efficacy, exosomes offer enhanced delivery of cargoes in vivo. However, several challenges related to the stabilization of the exosomes, the production of sufficient amounts of exosomes with safety and efficacy, the efficient loading of drugs into exosomes, the clearance of exosomes from circulation, and the transition from the bench scale to clinical production may limit their development and clinical use. For the clinical use of exosomes, it is important to understand the molecular mechanisms behind the transport and function of exosome vesicles. This review exploits techniques related to the isolation and characterization of exosomes and their drug delivery potential to enhance the therapeutic outcome and stabilization methods. Further, routes of administration, clinical trials, and regulatory aspects of exosomes will be discussed in this review.

Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine: A Comprehensive Review

“…Research in the field of exosomes/extracellular vesicles is emerging, and extensive research is needed for future therapeutic applications. It also warrants the attention of researchers worldwide owing to its ability to transfer therapeutics to recipient cells via an endogenous uptake mechanism; therefore, the exosome vesicle is a promising candidate [ 150 ]. Although liposomes are a well-standardized drug delivery system, we strongly believe that the naturally secreted exosomes will stand as a promising therapeutic candidate in a wide spectrum of human diseases with incoming decades.…”

Designer Exosomes: Smart Nano-Communication Tools for Translational Medicine

“…MiR-218 is a crucial molecule in the signal-amplification circuit-dependent mechanism during osteogenic differentiation in human adipose tissue-derived stem cell differentiation [ 26 ]. The role of ncRNAs as therapeutics for musculoskeletal diseases, including osteoarthritis, rheumatoid arthritis, and muscular dystrophies have been identified [ 25 , 56 ]. However, the precise mechanisms of delivering the ncRNAs to the target tissues remain to be investigated.…”

Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation

“…For CNS applications, this lends itself towards neurodegeneration or traumatic brain injury where modulating inflammation can be beneficial. However, exosomes can be modified into tumor-killing agents, via modification of the parent cell, such as overexpression of miRNAs which inhibit cell growth or inhibit angiogenesis [ 122 ]. Alternatively, exosomes can be loaded with exogenous products and thus can serve as drug and gene delivery vehicles.…”

“…As described earlier, the efficiency of different cell-derived exosomes in BBB crossing also varies widely and it is unclear what parameters can be used to screen exosomes for likelihood of BBB permeability. Exosome circulatory properties are also not ideal for chemotherapy treatments, since their circulatory half-life is approximately two minutes [ 122 , 129 ].…”