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Penetration of the blood-brain barrier and anti-tumor effect of a novel PLGA-lysoGM1/DOX micelles drug delivery system

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 comprised of PLGA-lysoGM1/DOX micelles was developed to across the BBB for CNS administration. 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 demonstrate that PLGA-lysoGM1/DOX micelles have a slow and sustainable drug release under physiological conditions and exhibit 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 across the BBB and specifically accumulated in the brain. Moreover, an excellent anti-glioma effect presented in intracranial glioma‐bearing rat. Therefore, PLGA-lysoGM1/DOX micelles not only effectively acrossed the BBB, but our results suggest it has a great potential for anti-glioma therapy and other central nervous system diseases.

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Supplementary files

Article information


Submitted
11 Oct 2019
Accepted
23 Dec 2019
First published
07 Jan 2020

Nanoscale, 2020, Accepted Manuscript
Article type
Communication

Penetration of the blood-brain barrier and anti-tumor effect of a novel PLGA-lysoGM1/DOX micelles drug delivery system

Y. Wang, Y. Yin, J. Wang, M. Yang, R. Du, G. Pontrelli, S. McGinty, G. Wang and T. Yin, Nanoscale, 2020, Accepted Manuscript , DOI: 10.1039/C9NR08741A

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