Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Resea...

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Autores principales:	Harigae T, Nakagawa K, Miyazawa T, Inoue N, Kimura F, Ikeda I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	absorption metabolism bioavailability mixed micelles Caco-2 HPLC-MS/MS Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/25d495c4da014149949988b5aba9e817
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spelling	oai:doaj.org-article:25d495c4da014149949988b5aba9e8172021-12-02T07:13:43ZMetabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration1178-2013https://doaj.org/article/25d495c4da014149949988b5aba9e8172016-06-01T00:00:00Zhttps://www.dovepress.com/metabolic-fate-of-poly-lactic-co-glycolic-acid-based-curcumin-nanopart-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 3Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: 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.Conclusion: 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. Keywords: absorption, metabolism, bioavailability, mixed micelles, Caco-2, HPLC-MS/MSHarigae TNakagawa KMiyazawa TInoue NKimura FIkeda IMiyazawa TDove Medical Pressarticleabsorptionmetabolismbioavailabilitymixed micellesCaco-2HPLC-MS/MSMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3009-3022 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	absorption metabolism bioavailability mixed micelles Caco-2 HPLC-MS/MS Medicine (General) R5-920
spellingShingle	absorption metabolism bioavailability mixed micelles Caco-2 HPLC-MS/MS Medicine (General) R5-920 Harigae T Nakagawa K Miyazawa T Inoue N Kimura F Ikeda I Miyazawa T Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
description	Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 3Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: 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.Conclusion: 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. Keywords: absorption, metabolism, bioavailability, mixed micelles, Caco-2, HPLC-MS/MS
format	article
author	Harigae T Nakagawa K Miyazawa T Inoue N Kimura F Ikeda I Miyazawa T
author_facet	Harigae T Nakagawa K Miyazawa T Inoue N Kimura F Ikeda I Miyazawa T
author_sort	Harigae T
title	Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
title_short	Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
title_full	Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
title_fullStr	Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
title_full_unstemmed	Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
title_sort	metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/25d495c4da014149949988b5aba9e817
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_version_	1718399507526320128

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

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