title: A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation.
abstract: Plant-derived polyphenols such as curcumin hold promise as a therapeutic agent in the treatment of chronic liver diseases. However, its development is plagued by poor aqueous solubility resulting in poor bioavailability. To circumvent the suboptimal bioavailability of free curcumin, we have developed a polymeric nanoparticle formulation of curcumin (NanoCurc™) that overcomes this major pitfall of the free compound. In this study, we show that NanoCurc™ results in sustained intrahepatic curcumin levels that can be found in both hepatocytes and non-parenchymal cells. NanoCurc™ markedly inhibits carbon tetrachloride-induced liver injury, production of pro-inflammatory cytokines and fibrosis. It also enhances antioxidant levels in the liver and inhibits pro-fibrogenic transcripts associated with activated myofibroblasts. Finally, we show that NanoCurc™ directly induces stellate cell apoptosis in vitro. Our results suggest that NanoCurc™ might be an effective therapy for patients with chronic liver disease.
authors.affiliation: Department of Pathology, Division of GI and Liver Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Bisht
authors.forename: Mehtab A
authors.initials: MA
authors.lastname: Khan
authors.forename: Mena
authors.initials: M
authors.lastname: Bekhit
authors.forename: Haibo
authors.initials: H
authors.lastname: Bai
authors.forename: Toby
authors.initials: T
authors.lastname: Cornish
authors.forename: Masamichi
authors.initials: M
authors.lastname: Mizuma
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Amarnath
authors.initials: A
authors.lastname: Maitra
authors.forename: Balmiki
authors.initials: B
authors.lastname: Ray
authors.forename: Debomoy
authors.initials: D
authors.lastname: Lahiri
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
mesh_terms: D000818:Animals; D001682:Biological Availability; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000517:prevention & control*; D002461:Cell Line, Transformed; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018836:Inflammation Mediators; D003474:Curcumin