Challenges in the Development of Drug Delivery Systems Based on Small Extracellular Vesicles for Therapy of Brain Diseases

Abstract

Small extracellular vesicles (sEVs) have ∼30–200 nm diameter size and may act as carriers of different cargoes, depending on the cell of origin or on the physiological/pathological condition. As endogenous nanovesicles, sEVs are important in intercellular communication and have many of the desirable features of an ideal drug delivery system. sEVs are naturally biocompatible, with superior targeting capability, safety profile, nanometric size, and can be loaded with both lipophilic and hydrophilic agents. Because of their biochemical and physical properties, sEVs are considered a promising strategy over other delivery vehicles in the central nervous system (CNS) since they freely cross the blood-brain barrier and they can be directed to specific nerve cells, potentiating a more precise targeting of their cargo. In addition, sEVs remain stable in the peripheral circulation, making them attractive nanocarrier systems to promote neuroregeneration. This review focuses on the recent progress in methods for manufacturing, isolating, and engineering sEVs that can be used as a therapeutic strategy to overcome neurodegeneration associated with pathologies of the CNS, with particular emphasis on Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis diseases, as well as on brain tumors.

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer’s Disease

“…Recently, more and more studies have focused on the enrichment of plasma exosomes into microglia ( Fitzner et al, 2011 ; Ginini et al, 2022 ; Loch-Neckel et al, 2022 ). Microglia, resident immune cells in the brain, engulf dead cells and help clear out misfolded aggregates of proteins, such as amyloid plaques in AD.…”

The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications

“…Many studies have shown that EVs are transported over the BBB and reach the periphery; however, the underlying mechanism remains unclear, and evidence is sparse (Pegtel et al, 2014 ; Yáñez-Mó et al, 2015 ; Saint-Pol et al, 2020 ). Recent studies have shown that anti-inflammatory drugs could be delivered to the mice's brains through intranasal injection of EVs, indicating that EV administration to the CNS is feasible (Zhuang et al, 2011 ; Loch-Neckel et al, 2022 ). Similarly, the systemic administration has also exploited EVs to transfer small-interfering RNA molecules to mice brains (Cooper et al, 2014 ).…”

Roles of small extracellular vesicles in the development, diagnosis and possible treatment strategies for hepatocellular carcinoma (Review)

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