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: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2013
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/f6f8e8ad7911456fbacc71913c3fefff |
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| Sumario: | 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 |
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