title: Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.
abstract: OBJECTIVE
  Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability.
  
  
  METHODS
  Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells.
  
  
  RESULTS
  Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo.
  
  
  CONCLUSIONS
  These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Harigae
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Taiki
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science.
authors.forename: Nao
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kimura
authors.affiliation: Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ikeda
authors.affiliation: Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center; Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D008823:Micelles; C096277:tetrahydrocurcumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin
keywords: Caco-2; HPLC-MS/MS; absorption; bioavailability; metabolism; mixed micelles