PUBLICATION
Penetration of the blood-brain barrier and the anti-tumour effect of a novel PLGA-lysoGM1/DOX micelle drug delivery system
- Authors
- Yin, Y., Wang, J., Yang, M., Du, R., Pontrelli, G., McGinty, S., Wang, G., Yin, T., Wang, Y.
- ID
- ZDB-PUB-200130-11
- Date
- 2020
- Source
- Nanoscale 12(5): 2946-2960 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Blood-Brain Barrier/metabolism*
- Blood-Brain Barrier/pathology
- Brain Neoplasms/drug therapy*
- Brain Neoplasms/metabolism
- Brain Neoplasms/pathology
- Doxorubicin*/pharmacokinetics
- Doxorubicin*/pharmacology
- Drug Delivery Systems*
- G(M1) Ganglioside/analogs & derivatives*
- G(M1) Ganglioside/pharmacokinetics
- G(M1) Ganglioside/pharmacology
- Glioma/drug therapy*
- Glioma/metabolism
- Glioma/pathology
- Humans
- Male
- Mice
- Micelles
- Polylactic Acid-Polyglycolic Acid Copolymer*/pharmacokinetics
- Polylactic Acid-Polyglycolic Acid Copolymer*/pharmacology
- Zebrafish
- PubMed
- 31994576 Full text @ Nanoscale
Citation
Yin, Y., Wang, J., Yang, M., Du, R., Pontrelli, G., McGinty, S., Wang, G., Yin, T., Wang, Y. (2020) Penetration of the blood-brain barrier and the anti-tumour effect of a novel PLGA-lysoGM1/DOX micelle drug delivery system. Nanoscale. 12(5):2946-2960.
Abstract
Effective treatment of glioma and other central nervous system (CNS) diseases is hindered by the presence of the blood-brain barrier (BBB). A novel nano-delivery vehicle system composed of PLGA-lysoGM1/DOX micelles was developed to cross the BBB for CNS treatment. We have shown that doxorubicin (DOX) as a model drug encapsulated in PLGA-lysoGM1 micelles can achieve up to 3.8% loading efficiency and 61.6% encapsulation efficiency by the orthogonal test design. Our in vitro experiments demonstrated that PLGA-lysoGM1/DOX micelles had a slow and sustainable drug release under physiological conditions and exhibited a high cellular uptake through the macropinocytosis and the autophagy/lysosomal pathways. In vivo experimental studies in zebrafish and mice confirmed that PLGA-lysoGM1/DOX micelles could cross the BBB and be specifically accumulated in the brain. Moreover, an excellent anti-glioma effect was observed in intracranial glioma-bearing rats. Therefore, PLGA-lysoGM1/DOX micelles not only effectively can cross the BBB, but our results also suggest that they have great potential for anti-glioma therapy and other central nervous system diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping