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...
Guardado en:
Autores principales: | , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Dove Medical Press
2013
|
Materias: | |
Acceso en línea: | https://doaj.org/article/f6f8e8ad7911456fbacc71913c3fefff |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:f6f8e8ad7911456fbacc71913c3fefff |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT xiaoy synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo AT zhangh synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo AT zhangz synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo AT yanm synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo AT leim synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo AT zengk synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo AT zhaoc synthesisofnoveltetravalentgalactosylateddtpadspeandstudyonhepatocytetargetingefficiencyinvitroandinvivo |
_version_ |
1718401074459574272 |