title: Characterization and biological properties of NanoCUR formulation and its effect on major human cytochrome P450 enzymes.
abstract: Curcumin (CUR) has been formulated into a host of nano-sized formulations in a bid to improve its in vivo solubility, stability and bioavailability. The aim of this study was to investigate whether the encapsulation of CUR in nanocarriers would impede its biological interactivity, specifically its potential anti-cancer adjuvant activity via the modulation of CYP enzymes in vitro. NanoCUR, a micellar dispersion prepared via a thin film method using only Pluronic F127 as excipient, was amenable to lyophilization, and retained its nano-sized spherical dimensions (17-33 nm) upon reconstitution with water followed by dilution to 5 μM with HBSS or EMEM. NanoCUR was a weaker cytotoxic agent compared to CUR in solution (sCUR), affecting HepG2 cell viability only when the incubation time was prolonged from 4h to 48 h. Correlation with 2h uptake data suggests this was due to a lower cellular uptake rate of CUR from NanoCUR than from sCUR. The poorer CUR accessibility might also account for NanoCUR being a weaker inhibitor of CYP2C9 and CYP2D6 than sCUR. NanoCUR was, however, 1.76-fold more potent against the CYP3A4 (IC50 5.13 ± 0.91 μM) metabolic function. The higher activity against CYP3A4 might be attributed to the synergistic action of Pluronic F127, since the blank micellar dispersion also inhibited CYP3A4 activity. Both sCUR and NanoCUR had no effect on the CYP3A4 mRNA levels in the HepG2 cells. NanoCUR therefore, maintained most of the biological activities of CUR in vitro, albeit at a lower potency and response rate.
authors: Laboratory for Drug Delivery, Pharmacy, School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Highway, Crawley 6009, Western Australia, Australia; Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
authors: Suhaili
authors: S
authors: Shamsi
authors: School of Pharmacy, CHIRI Biosciences, Curtin University, Bentley, 6102, Western Australia, Australia.
authors: Yan
authors: Y
authors: Chen
authors: Laboratory for Drug Delivery, Pharmacy, School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Highway, Crawley 6009, Western Australia, Australia. Electronic address: lee.lim@uwa.edu.au.
authors: Lee Yong
authors: LY
authors: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004337:Drug Carriers / Q000737:chemistry*; D004794:Enzyme Repression; D056945:Hep G2 Cells; D006801:Humans; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D020442:Poloxamer; D003577:Cytochrome P-450 Enzyme System; D003474:Curcumin
keywords: Curcumin; Cytochrome P450; NanoCUR; Pluronic F127