Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease Articles uri icon

authors

  • ALBALADEJO GARCIA, VIRGINIA
  • MORAN, LAURA
  • SANTOS COQUILLAT, ANA MARIA
  • GONZALEZ GUTIERREZ, MARIA ISABEL
  • YE, HUI
  • VAZQUEZ OGANDO, ELENA
  • VAQUERO, JAVIER
  • CUBERO, FRANCISCO JAVIER
  • DESCO MENENDEZ, MANUEL
  • SALINAS, BEATRIZ

publication date

  • April 2024

start page

  • 116381

volume

  • 173

International Standard Serial Number (ISSN)

  • 0753-3322

Electronic International Standard Serial Number (EISSN)

  • 1950-6007

abstract

  • 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±5.1nm, sEVCurPas: 127.0±4.5nm and sEVCurAc: 98.5±3.6nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5µg/mL) in comparison with the passive approach (129.1µg/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) (557U/L to 338U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition.

subjects

  • Biology and Biomedicine

keywords

  • nanoparticle; exosome; curcumin; drug delivery system; hepatic disease; extracellular vesicle