A green approach to treating neurological conditions: the promise of plant-derived exosome-like nanovesicles.

Abstract

Plant-derived exosome-like nanovesicles (PELNs) are being investigated as bioactive preparations and drug carriers for neurological disorders. However, preparations recovered from disrupted plant tissues are heterogeneous and should not automatically be equated with naturally secreted extracellular vesicles or endosome-derived exosomes. This narrative review critically examines vesicle identity, isolation and purification, cellular uptake, brain delivery, disease-specific evidence, and translational requirements. Ultracentrifugation, size exclusion chromatography, polymer precipitation, and microfluidic approaches offer different trade-offs between recovery, contaminant removal, throughput, and scalability. Preclinical studies report effects in ischemic injury, glioma, amyloid-related models, Parkinsonian models, and gut-brain signaling, but these findings depend on the plant source, formulation, administration route, and experimental model. Endothelial uptake, transport across an intact blood-brain barrier, entry through a damaged barrier, and intranasal delivery represent distinct processes. Fluorescent tissue accumulation alone does not establish delivery of intact vesicles or functional cargo. Recent negative and cell-selective findings further challenge the assumption that all PELNs are effective neuronal carriers. Clinical development requires quantitative pharmacokinetics, route-specific biodistribution, repeated-dose safety assessment, causal cargo validation, and reproducible manufacturing with potency-linked release specifications. PELNs therefore provide a promising research platform rather than an established class of safe, intrinsically brain-targeting therapeutics. Their proposed environmental and commercial advantages also require direct process, cost, and life-cycle evaluation.

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