title: Influence of particle size on the in vitro and in vivo anti-inflammatory and anti-allergic activities of a curcumin lipid nanoemulsion.
abstract: The polyphenolic compound, curcumin, is a natural yellow pigment component of turmeric. It exerts various biological effects, such as anti-inflammatory effects, and we have previously demonstrated that curcumin is a specific inhibitor of DNA polymerase λ. Curcumin is characterized by poor bioavailability as it is water-insoluble, is poorly absorbed and is systemically eliminated. In order to increase the bioavailability of curcumin, in this study, we produced a curcumin-loaded lipid nanoemulsion of various particle sizes (50, 100 and 200 nm). The curcumin lipid nanoemulsion was prepared by a modified thin-film hydration method followed by sonication. To identify the optimal particle size which exhibits the strongest physiological activity, we investigated the inhibitory effects of the obtained nanoemulsions against inflammatory and allergic activities. In in vitro cell culture experiments, the 100-nm curcumin lipid nanoemulsion showed the most prominent inhibitory effect on the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW264.7 murine macrophages, and on the release of β-hexosaminidase induced by the calcium ionophore, A23187, in rat basophilic leukemia RBL-2H3 cells. In an in vivo experiment, in which mice were administered the curcumin-loaded lipid nanoemulsion of various particle sizes, the 100-nm curcumin lipid nanoemulsion showed the most prominent anti-inflammatory and anti-allergic effects, inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema and immunoglobulin E (IgE)-induced passive cutaneous anaphylactic (PCA) reaction. The effects of particle size on serum curcumin absorption were also assessed in mice, and the 100-nm lipid nanoemulsion showed the greatest absorption. The results from our study suggest that the physiological activities of curcumin lipid nanoemulsions differ depending on particle size. Our data indicate that the curcumin lipid nanoemulsion with a particle size of 100 nm has potential for use in enhancing the bioavailability and medical value of curcumin.
authors.affiliation: Laboratory of Food and Nutritional Sciences, Faculty of Nutrition, Kobe Gakuin University, Kobe, Hyogo 651-2180, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe, Hyogo 651-8586, Japan.
authors.forename: Isoko
authors.initials: I
authors.lastname: Kuriyama
authors.affiliation: Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe, Hyogo 651-8586, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Andoh
authors.affiliation: Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe, Hyogo 651-8586, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Laboratory of Food and Nutritional Sciences, Faculty of Nutrition, Kobe Gakuin University, Kobe, Hyogo 651-2180, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe, Hyogo 651-8586, Japan.
authors.forename: Eibai
authors.initials: E
authors.lastname: Lee-Hiraiwa
authors.affiliation: Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe, Hyogo 651-8586, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004655:Emulsions; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D004655:Emulsions; D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate