Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics

Jing Zhao,1,&ast; Qing Zhao,1,&ast; Jing-Ze Lu,1 Dan Ye,1 Sheng Mu,1 Xiao-Di Yang,2 Wei-Dong Zhang,3,4 Bing-Liang Ma1 1Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional...

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Autores principales:	Zhao J, Zhao Q, Lu JZ, Ye D, Mu S, Yang XD, Zhang WD, Ma BL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	natural nanoparticles drug delivery system pharmacokinetic synergy berberine hydrochloride herbal extract Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d2848fe95f784545b98789d158fc79f6
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spelling	oai:doaj.org-article:d2848fe95f784545b98789d158fc79f62021-12-02T19:14:26ZNatural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics1178-2013https://doaj.org/article/d2848fe95f784545b98789d158fc79f62021-09-01T00:00:00Zhttps://www.dovepress.com/natural-nano-drug-delivery-system-in-coptidis-rhizoma-extract-with-mod-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Jing Zhao,1,&ast; Qing Zhao,1,&ast; Jing-Ze Lu,1 Dan Ye,1 Sheng Mu,1 Xiao-Di Yang,2 Wei-Dong Zhang,3,4 Bing-Liang Ma1 1Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Second Military Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Dong Zhang; Bing-Liang Ma Email wdzhangy@hotmail.com; bingliang.ma@hotmail.comPurpose: This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms.Methods: Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied.Results: The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of − 12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (Cmax, 1182.3 vs 310.2 ng/mL) and exposure level (AUC0– 12 h, 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver).Conclusion: The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.Keywords: natural nanoparticles, drug delivery system, pharmacokinetic synergy, berberine hydrochloride, herbal extractZhao JZhao QLu JZYe DMu SYang XDZhang WDMa BLDove Medical Pressarticlenatural nanoparticlesdrug delivery systempharmacokinetic synergyberberine hydrochlorideherbal extractMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 6297-6311 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	natural nanoparticles drug delivery system pharmacokinetic synergy berberine hydrochloride herbal extract Medicine (General) R5-920
spellingShingle	natural nanoparticles drug delivery system pharmacokinetic synergy berberine hydrochloride herbal extract Medicine (General) R5-920 Zhao J Zhao Q Lu JZ Ye D Mu S Yang XD Zhang WD Ma BL Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics
description	Jing Zhao,1,&ast; Qing Zhao,1,&ast; Jing-Ze Lu,1 Dan Ye,1 Sheng Mu,1 Xiao-Di Yang,2 Wei-Dong Zhang,3,4 Bing-Liang Ma1 1Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Second Military Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Dong Zhang; Bing-Liang Ma Email wdzhangy@hotmail.com; bingliang.ma@hotmail.comPurpose: This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms.Methods: Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied.Results: The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of − 12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (Cmax, 1182.3 vs 310.2 ng/mL) and exposure level (AUC0– 12 h, 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver).Conclusion: The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.Keywords: natural nanoparticles, drug delivery system, pharmacokinetic synergy, berberine hydrochloride, herbal extract
format	article
author	Zhao J Zhao Q Lu JZ Ye D Mu S Yang XD Zhang WD Ma BL
author_facet	Zhao J Zhao Q Lu JZ Ye D Mu S Yang XD Zhang WD Ma BL
author_sort	Zhao J
title	Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics
title_short	Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics
title_full	Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics
title_fullStr	Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics
title_full_unstemmed	Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics
title_sort	natural nano-drug delivery system in coptidis rhizoma extract with modified berberine hydrochloride pharmacokinetics
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/d2848fe95f784545b98789d158fc79f6
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Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics

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