Nanocurcumin Formulation Increases Bioavailability of Curcumin and Prevents Experimentally Induced Liver Fibrosis
M Khan, S Bisht, A Maitra, RA Anders. The Johns Hopkins School of Medicine, Baltimore, MD
Background: Chronic liver disease is a leading cause of death worldwide. Liver fibrosis is a hallmark of chronic liver disease. There are few treatment options for preventing progressive chronic liver disease. The natural product curcumin is a polyphenol extract from the spice turmeric which has been shown to prevent liver fibrosis in mice. However, these studies are hampered by requiring ingestion of megadoses of curcumin which still results in poor bioavailability. We have developed a nanoparticle formulation of curcumin, nanocurcumin (NC), which is fully soluble in aquoues media. We wish to test if NC increases bioavailability of curcumin and can prevent liver fibrosis in mice.
Design: Pharmakokinetics: Two formulations, one of NC and the other of free curcumin (FC) in corn oil were administered through the intraperitoneal (i.p.) route as a single dose of 25mg/kg to 6 mice each. The level of curcumin in the blood was measured by HPLC at 1, 2, 4, 8, and 24 hours. Fibrosis: Mice (n=5-10/group) were treated with aqueous NC 25mg/kg or control i.p. injection every other day for 2 weeks. Carbon tetrachloride in oil or control oil was given twice /wk i.p. over 2 weeks. Liver tissue was harvested for sirus red staining, hydroxyproline (collagen) content and serum collected for alanine aminotransferase (ALT) enzymatic assay and TNFalpha ELISA.
Results: Pharmakokinetics: We found curcumin levels peaked in the serum at 5 hrs and persisted 20 hrs post NC injection, while FC was not detectable at all time points. No toxicities were noted. Fibrosis:
|Sirus red||Bridging fibrosis||Portal fibrosis*|
|Hydroxyoproline||250 +/- 20||130 +/- 25*|
|Serm ALT||300 +/- 75||175 +/- 100*|
|Serum TNF alpha||120 +/- 35||non-detectable*|