Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study

Ling-Chun Chen,1,* Ying-Chen Chen,1,* Chia-Yu Su,1 Chung-Shu Hong,1 Hsiu-O Ho,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan *Thes...

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Autores principales:	Chen LC, Chen YC, Su CY, Hong CS, Ho HO, Sheu MT
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	quercetin micelle lecithin Pluronic DSPE-PEG Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7b76b708f3fe4682aef834b30c23353b
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spelling	oai:doaj.org-article:7b76b708f3fe4682aef834b30c23353b2021-12-02T05:10:45ZDevelopment and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study1178-2013https://doaj.org/article/7b76b708f3fe4682aef834b30c23353b2016-04-01T00:00:00Zhttps://www.dovepress.com/development-and-characterization-of-self-assembling-lecithin-based-mix-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ling-Chun Chen,1,* Ying-Chen Chen,1,* Chia-Yu Su,1 Chung-Shu Hong,1 Hsiu-O Ho,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Quercetin (Que) is known to have biological benefits including an anticancer effect, but low water solubility limits its clinical application. The aim of this study was to develop a lecithin-based mixed polymeric micelle (LMPM) delivery system to improve the solubility and bioavailability of Que. The optimal Que-LMPM, composed of Que, lecithin, Pluronic® P123, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy[poly(ethylene glycol)-2000] in a proportion of 3:1:17.5:2.5 (w/w), was prepared by a thin-film method. The average size, polydispersion index, encapsulating efficiency, and drug loading of Que-LMPM were 61.60±5.02 nm, 0.589±0.198, 96.87%±9.04%, and 12.18%±1.11%, respectively. The solubility of Que in the Que-LMPM system increased to 5.81 mg/mL, compared to that of free Que in water of 0.17–7.7 µg/mL. The Que-LMPM system presented a sustained-release property in vitro. The in vitro cytotoxicity assay showed that the 50% inhibitory concentration values toward MCF-7 breast cancer cells for free Que, blank LMPMs, and Que-LMPMs were >200, >200, and 110 µM, respectively, indicating the nontoxicity of the LMPM carrier, but the LMPM formulation enhanced the cytotoxicity of Que against MCF-7 cells. A cellular uptake assay also confirmed the intake of Que-LMPM by MCF-7 cells. An in vivo pharmacokinetic study demonstrated that Que-LMPMs had higher area under the concentration–time curve and a longer half-life, leading to better bioavailability compared to a free Que injection. Due to their nanosize, core–shell structure, and solubilization potential, LMPMs were successfully developed as a drug delivery system for Que to improve its solubility and bioavailability. Keywords: quercetin, micelle, lecithin, Pluronic®, DSPE-PEG, mixed micelles, bioavailabilityChen LCChen YCSu CYHong CSHo HOSheu MTDove Medical PressarticlequercetinmicellelecithinPluronicDSPE-PEGMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1557-1566 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	quercetin micelle lecithin Pluronic DSPE-PEG Medicine (General) R5-920
spellingShingle	quercetin micelle lecithin Pluronic DSPE-PEG Medicine (General) R5-920 Chen LC Chen YC Su CY Hong CS Ho HO Sheu MT Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
description	Ling-Chun Chen,1,* Ying-Chen Chen,1,* Chia-Yu Su,1 Chung-Shu Hong,1 Hsiu-O Ho,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Quercetin (Que) is known to have biological benefits including an anticancer effect, but low water solubility limits its clinical application. The aim of this study was to develop a lecithin-based mixed polymeric micelle (LMPM) delivery system to improve the solubility and bioavailability of Que. The optimal Que-LMPM, composed of Que, lecithin, Pluronic® P123, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy[poly(ethylene glycol)-2000] in a proportion of 3:1:17.5:2.5 (w/w), was prepared by a thin-film method. The average size, polydispersion index, encapsulating efficiency, and drug loading of Que-LMPM were 61.60±5.02 nm, 0.589±0.198, 96.87%±9.04%, and 12.18%±1.11%, respectively. The solubility of Que in the Que-LMPM system increased to 5.81 mg/mL, compared to that of free Que in water of 0.17–7.7 µg/mL. The Que-LMPM system presented a sustained-release property in vitro. The in vitro cytotoxicity assay showed that the 50% inhibitory concentration values toward MCF-7 breast cancer cells for free Que, blank LMPMs, and Que-LMPMs were >200, >200, and 110 µM, respectively, indicating the nontoxicity of the LMPM carrier, but the LMPM formulation enhanced the cytotoxicity of Que against MCF-7 cells. A cellular uptake assay also confirmed the intake of Que-LMPM by MCF-7 cells. An in vivo pharmacokinetic study demonstrated that Que-LMPMs had higher area under the concentration–time curve and a longer half-life, leading to better bioavailability compared to a free Que injection. Due to their nanosize, core–shell structure, and solubilization potential, LMPMs were successfully developed as a drug delivery system for Que to improve its solubility and bioavailability. Keywords: quercetin, micelle, lecithin, Pluronic®, DSPE-PEG, mixed micelles, bioavailability
format	article
author	Chen LC Chen YC Su CY Hong CS Ho HO Sheu MT
author_facet	Chen LC Chen YC Su CY Hong CS Ho HO Sheu MT
author_sort	Chen LC
title	Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
title_short	Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
title_full	Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
title_fullStr	Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
title_full_unstemmed	Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
title_sort	development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/7b76b708f3fe4682aef834b30c23353b
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Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study

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