Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo

Yan Xiao, Huafang Zhang, Zhaoguo Zhang, Mina Yan, Ming Lei, Ke Zeng, Chunshun Zhao School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China Abstract: For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galacto...

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Autores principales: Xiao Y, Zhang H, Zhang Z, Yan M, Lei M, Zeng K, Zhao C
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:f6f8e8ad7911456fbacc71913c3fefff2021-12-02T04:46:20ZSynthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo1176-91141178-2013https://doaj.org/article/f6f8e8ad7911456fbacc71913c3fefff2013-08-01T00:00:00Zhttp://www.dovepress.com/synthesis-of-novel-tetravalent-galactosylated-dtpa-dspe-and-study-on-h-a14007https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yan Xiao, Huafang Zhang, Zhaoguo Zhang, Mina Yan, Ming Lei, Ke Zeng, Chunshun Zhao School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China Abstract: For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated into liposomes using an ammonium sulfate gradient loading method. The liposomal formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning microscopy and flow cytometry analysis, and the results demonstrated that the 4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of 4Gal-liposomes was higher than that of the conventional liposomes without the galactose. Additionally, pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed slower clearance from the systemic circulation compared with conventional liposomes. The organ distributions in mice and the study on frozen sections of liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX into hepatocytes and prolonged the circulation. Taken together, these results indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug delivery carriers for hepatocyte-selective targeting. Keywords: targeted drug delivery, liposomes, pharmacokinetics, galactose, ASGP-R, doxorubicinXiao YZhang HZhang ZYan MLei MZeng KZhao CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 3033-3050 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Xiao Y
Zhang H
Zhang Z
Yan M
Lei M
Zeng K
Zhao C
Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo
description Yan Xiao, Huafang Zhang, Zhaoguo Zhang, Mina Yan, Ming Lei, Ke Zeng, Chunshun Zhao School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China Abstract: For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated into liposomes using an ammonium sulfate gradient loading method. The liposomal formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning microscopy and flow cytometry analysis, and the results demonstrated that the 4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of 4Gal-liposomes was higher than that of the conventional liposomes without the galactose. Additionally, pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed slower clearance from the systemic circulation compared with conventional liposomes. The organ distributions in mice and the study on frozen sections of liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX into hepatocytes and prolonged the circulation. Taken together, these results indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug delivery carriers for hepatocyte-selective targeting. Keywords: targeted drug delivery, liposomes, pharmacokinetics, galactose, ASGP-R, doxorubicin
format article
author Xiao Y
Zhang H
Zhang Z
Yan M
Lei M
Zeng K
Zhao C
author_facet Xiao Y
Zhang H
Zhang Z
Yan M
Lei M
Zeng K
Zhao C
author_sort Xiao Y
title Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo
title_short Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo
title_full Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo
title_fullStr Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo
title_full_unstemmed Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo
title_sort synthesis of novel tetravalent galactosylated dtpa-dspe and study on hepatocyte-targeting efficiency in vitro and in vivo
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/f6f8e8ad7911456fbacc71913c3fefff
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