Dosing of plant-derived extracellular vesicles in traditional Chinese medicine: current status, root causes, and standardization pathways

Extracellular vesicles derived from Traditional Chinese Medicine represent a growing research Frontier. However, no consensus exists regarding the definition, quantification, and reporting of administered doses. This methodological issue continues to compromise study reproducibility. This article draws on a comprehensive analysis of recent and foundational literature on TCM-derived extracellular vesicles. Analysis shows marked differences in measurement units, reporting formats, and magnitude ranges for both in vitro and in vivo dosing. Vesicle yields also vary considerably depending on plant species, extraction method, and harvest season. The inconsistency of dose reporting and the incomparability of yield data together impede clinical translation. Further examination identifies three root causes: inherent fluctuations from batch-to-batch variability of herbal materials, the prolonged absence of quantitative standards for plant vesicles, and - as a core conceptual finding - the divergent dosing logic arising from the dual identity of vesicles as both pharmacologically active entities and nanocarriers. Based on these findings, this article proposes several standardization pathways. These include establishing multi-dimensional reporting norms for dose and yield, constructing species-specific efficacy equivalent systems, and bridging the metrological gap between traditional herbal dosage and modern nanomedicine dosing.