Mesenchymal stem cell-derived exosomes as nanocarriers for curcumin: from fundamental research to clinical translation

Curcumin has diverse pharmacological activities but poor water solubility, rapid degradation, extensive metabolism, and very low oral bioavailability limit its therapeutic use. This review evaluates mesenchymal stem cell-derived exosomes (MSC-Exo; MSC-derived small extracellular vesicles per MISEV2023) as natural nanocarriers for curcumin delivery and the barriers to clinical translation. Curcumin-loaded MSC-Exo (Cur@Exos) can improve curcumin stability, sustain release, enhance target-tissue accumulation, and cross biological barriers such as the blood-brain barrier. Compared with synthetic nanocarriers, MSC-Exo may offer better biocompatibility, immune evasion, and tissue tropism, but these properties depend on source and preparation; proteomes, miRNA cargoes, and functions differ among bone marrow-, umbilical cord-, and adipose-derived MSCs. Encapsulation efficiency, batch consistency, scalability, and storage stability also remain suboptimal. Preclinical studies show Cur@Exos benefits in neurodegenerative diseases, rheumatoid arthritis, liver disease, wound healing, bone defects, and sepsis-associated kidney injury. However, findings are limited by heterogeneity in exosome sources, preparation, loading methods, and animal models; small samples and short follow-up; inconsistent dose metrics (particle number vs. protein content); and lack of standardized process and outcome criteria, reference materials, and potency assays. Long-term safety remains inadequately established: current evidence covers only short-term single or repeated dosing; ≥ 6-month repeat-dose toxicology with anti-drug antibody and complement monitoring, predictive immunogenicity screening, tumorigenicity assessment, potency-based batch release testing, and clinical efficacy data are lacking. MSC-Exo is a promising curcumin-delivery platform, but translation requires standardized manufacturing, globally harmonized quality control, improved scalability, systematic safety evaluation, well-designed multicenter trials, and a clarified international regulatory pathway.