Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles

Exosomes and plant-derived exosome-like nanoparticles (PELNs) are increasingly investigated as biologically derived nanocarriers that can couple cargo protection with biointerface-enabled transport. From a pharmaceutics standpoint, their therapeutic performance is often cargo-governed (e.g., microRNAs and proteins) and is ultimately constrained by delivery determinants such as stability, biodistribution, cellular uptake, and intracellular trafficking. In this review, we compare animal-derived exosomes (ADEs) and PELNs through a formulation-centric lens, emphasizing how source-dependent molecular composition shapes critical delivery behaviors and translational feasibility. We reorganize representative preclinical evidence into pharmaceutics-relevant delivery scenarios—including systemic/vascular targeting, blood–brain barrier transport, oral gastrointestinal delivery, and tumor microenvironment modulation—to connect cargo identity with exposure-site interactions and pharmacodynamic outcomes. We further discuss engineering strategies for improving payload control, targeting precision, and dosing accuracy, including endogenous enrichment, exogenous loading, and surface functionalization, while highlighting scale-up and safety considerations introduced by modification. Finally, we delineate translational priorities required to advance exosome-based products toward clinical development: standardized dose metrics (particle- and cargo-normalized), quantitative PK/biodistribution–PD relationships, potency assays and critical quality attributes (CQAs), manufacturing consistency under GMP, and regulatory-compliant characterization. Collectively, this review reframes ADEs and PELNs as cargo-driven pharmaceutical delivery systems and provides a practical roadmap for translation, with particular attention to the oral and scalable potential of PELNs.