Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

Abstract

Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.

Extracellular Vesicle-Based Therapy for COVID-19: Promises, Challenges and Future Prospects

“…Secondly, they enhance tissue or cell-specificity for targeted delivery. In order to enhance the targeted delivery and biodistribution of therapeutic components to particular sites in the human body, engineered EVs can be anchored with specific peptides that recognize specific cell surfaces in target tissues [148]. Along with their natural anti-inflammatory effects, these engineered EVs suppress viral replication in host cells, and reduce the cytokine storm and ARDS associated with COVID-19 patients [149].…”

“…To overcome this, coating of EVs with synthetic materials such as polyethylene glycol or streptavidin have been shown to increase vesicle bioavailability and extravasation capacity, and thus could increase their accumulation in lung tissue affected by COVID-19. Engineered EVs with certain specific proteins or peptides have exhibited the ability to increase the tissue specificity of EVs, which might help us better comprehend such customized treatment approaches in the future [148].…”

Skin Immunomodulation during Regeneration: Emerging New Targets

“…ADSCs derived exosomes rather than the MSCs or their conditioned media improved neutrophils viability and functions and seems to be more beneficial in infections and immunodeficiency diseases [ 66 ]. Many advancements have recently paved the way to animal studies to investigate the role of ADSCs derived exosomes or from other sources as drug delivery systems [ 67 ]. Engineering approaches are performed to ensure bioavailability of safe and efficient ADSCs and bone marrow derived exosomes for immunomodulatory activity [ 68 ].…”

Characterization and Therapeutic Use of Extracellular Vesicles Derived from Platelets

“…Recently, there has been great interest in the use of EVs from various cell types as therapeutic tools in human and veterinary medicine [ 50 , 51 , 52 , 53 ]. As concentrated platelets by means of PRP possess reparative and healing machinery, it is expected that PL-EVs might exhibit similar beneficial therapeutic properties under normal conditions due to their molecular cargo.…”