title: Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability.
abstract: OBJECTIVE
  The aim of the present study was to blend liquid lipids with solid lipids to encapsulate curcumin in solid lipid nanoparticles (SLNs), thereby improving the dispersibility and chemical stability of curcumin, prolonging its antitumour activity and cellular uptake and enhancing its bioavailability.
  
  
  METHODS
  Curcumin-loaded SLNs (C-SLNs) were prepared by high-pressure homogenisation with liquid lipid Sefsol-218(®). The morphology, stability and release of curcumin in the optimised formulation were investigated. The anti-cancer activity of the formulation was evaluated in MCF-7 cells. Fluorescence spectrophotometry was used to quantify cellular uptake of the drug. The pharmacokinetic profiles of curcumin in SLNs after intravenous administration were studied in rats.
  
  
  RESULTS
  Blending Sefsol-218(®) into a lipid matrix reduced the particle size without improving drug loading. An optimised formulation consisting of Dynasan 114(®), Sefsol-218(®), and Pluronic F68(®) (630:70:300, w/w) loaded with 0.8% drug was prepared. This formulation could be dispersed in water with a mean particle size of 152.8 ± 4.7 nm and a 90% entrapment efficiency. Curcumin displayed a two-phase sustained release profile from C-SLNs with improved chemical stability. Compared to the solubilised solution, C-SLNs exhibited prolonged inhibitory activity in cancer cells, as well as time-dependent increases in intracellular uptake. After intravenous administration to rats, the bioavailability of curcumin was increased by 1.25-fold.
  
  
  CONCLUSIONS
  C-SLNs with improved dispersibility and chemical stability in an aqueous system have been successfully developed. C-SLNs may represent a potentially useful cancer therapeutic curcumin delivery system.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China; National Institute for Food and Drug Control, Beijing, China.
authors.forename: Jiabei
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Hok Man
authors.initials: HM
authors.lastname: Chan
authors.affiliation: School of Chemistry & Chemical Engineering & Materials Science, Heilongjiang University, Harbin, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. Electronic address: yzheng@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D014867:Water; D003474:Curcumin
keywords: Bioavailability; Cellular uptake; Curcumin; Sefsol-218(®); Solid lipid nanoparticles (SLNs); Stability