Microneedle-Delivered Plant-Derived Exosome-like Nanovesicles for Dermatological Diseases: A Comprehensive Review

Plant-derived extracellular vesicle-like nanovesicles (PELNs) are being investigated as plant-derived preparations with intrinsic bioactivity and potential utility as nanocarriers. Microneedles (MNs) can create transient skin microchannels and may support localized intradermal delivery of vesicle-containing formulations. The intersection of these approaches is promising, but the available evidence remains heterogeneous and includes direct PELN-MN studies, PELN studies without MNs, and related mammalian extracellular vesicle platforms. Here we provide a comprehensive review of PELN identity, isolation, characterization, cargo, and proposed dermatological activities, followed by an assessment of MN designs relevant to vesicle delivery. We searched PubMed, Web of Science, Scopus, and Embase, screened records in duplicate, and classified each included study by the directness of evidence into studies providing direct PELN-MN skin evidence, PELN evidence without MNs, mammalian extracellular vesicle MN analogue evidence, and non-dermatological or conceptual evidence. Current limitations include uncertain vesicle identity, co-isolated plant constituents, variable preparation and dosing methods, limited controls for the mechanical effects of microneedling, and incomplete clinical follow-up. Progress toward translation will require source-specific quality attributes, orthogonal potency assays, transparent comparators, and adequately controlled clinical studies.