RT Journal Article
T1 Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease
A1 Albadalejo-García, Virginia
A1 Morán, Laura
A1 Santos-Coquillat, Ana
A1 González, María I.
A1 Ye, Hui
A1 Vázquez Ogando, Elena
A1 Salinas, Beatriz
A1 Vaquero Martín, Francisco Javier
A1 Cubero Palero, Francisco Javier
AB Curcumin is a natural molecule widely tested in preclinical and clinical studies due to its antioxidant and anti-inflammatory activity. Nevertheless, its high hydrophobicity and low bioavailability limit in vivo applications. To overcome curcumin´s drawbacks, small extracellular vesicles (sEVs) have emerged as potential drug delivery systems due to their non-immunogenicity, nanometric size and amphiphilic composition. This work presents curcumin cargo into milk sEV structure and further in vitro and in vivo evaluation as a therapeutic nanoplatform. The encapsulation of curcumin into sEV was performed by two methodologies under physiological conditions: a passive incorporation and active cargo employing saponin. Loaded sEVs (sEVCurPas and sEVCurAc) were fully characterized by physicochemical techniques, confirming that neither methodology affects the morphology or size of the nanoparticles (sEV: 113.3±5.1 nm, sEVCurPas: 127.0±4.5 nm and sEVCurAc: 98.5±3.6 nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5 µg/mL) in comparison with the passive approach (129.1 µg/mL). These sEVCurAc were further evaluated in vitro by metabolic activity assay (MTT), confocal microscopy, and flow cytometry, showing a higher cytotoxic effect in the tumoral cells RAW264.7 and HepG2 than in primary hepatocytes, specially at high doses of sEVCurAc (4%, 15% and 30% of viability). In vivo evaluation in an experimental model of liver fibrosis confirmed sEVCurAc therapeutic effects, leading to a significant decrease of serum markers of liver damage (ALT) (557 U/L to 338 U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition.
PB Elsevier
SN 0753-3322
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/102316
UL https://hdl.handle.net/20.500.14352/102316
LA eng
NO Albaladejo-García V, Morán L, Santos-Coquillat A, González MI, Ye H, Vázquez Ogando E, Vaquero J, Cubero FJ, Desco M, Salinas B. Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease. Biomed Pharmacother. 2024 Mar 6;173:116381. doi: 10.1016/j.biopha.2024.116381. Epub ahead of print. PMID: 38452655.
DS Docta Complutense
RD 2 sept 2025