PUBLICATION
Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system
- Authors
- Zou, D., Wang, W., Lei, D., Yin, Y., Ren, P., Chen, J., Yin, T., Wang, B., Wang, G., Wang, Y.
- ID
- ZDB-PUB-170727-5
- Date
- 2017
- Source
- International Journal of Nanomedicine 12: 4879-4889 (Journal)
- Registered Authors
- Lei, Daoxi, Wang, Guixue
- Keywords
- GM1, blood–brain barrier, doxorubicin, glioma, nanovesicles, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antibiotics, Antineoplastic/administration & dosage
- Antibiotics, Antineoplastic/pharmacology
- Blood-Brain Barrier/drug effects*
- Brain Neoplasms/drug therapy*
- Doxorubicin/administration & dosage
- Doxorubicin/pharmacokinetics
- Doxorubicin/pharmacology*
- Drug Delivery Systems/methods
- G(M1) Ganglioside/chemistry*
- Gangliosides/chemistry
- Glioma/drug therapy*
- Human Umbilical Vein Endothelial Cells
- Humans
- Male
- Micelles
- Nerve Regeneration/drug effects
- Rats, Wistar
- Tissue Distribution
- Zebrafish/genetics
- PubMed
- 28744122 Full text @ Int. J. Nanomedicine
Citation
Zou, D., Wang, W., Lei, D., Yin, Y., Ren, P., Chen, J., Yin, T., Wang, B., Wang, G., Wang, Y. (2017) Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system. International Journal of Nanomedicine. 12:4879-4889.
Abstract
For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping