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

Yin, Y., Wang, J., Yang, M., Du, R., Pontrelli, G., McGinty, S. , Wang, G., Yin, T. and Wang, Y. (2020) Penetration of the blood-brain barrier and anti-tumor effect of a novel PLGA-lysoGM1/DOX micelles drug delivery system. Nanoscale, 12, pp. 2946-2960. (doi: 10.1039/C9NR08741A) (PMID:31994576)

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.

• Item Type: Articles
• Additional Information: This work was supported by grants from the Natural Science Foundation Project of CQ CSTC (cstc2019jcyj-msxmX0307, cstc2019jcyj-zdxmX0009); the National Key Basic Research Project (973) (2014CB541600); the Fundamental Research Funds for the Central Universities (2019CDXYSG0004, 2019CDYGZD002); the National Key Research and Development Program of China (2016YFC1102305, 2018YFC0114408); the National Natural Science Foundation of China (11572064); and the support from the Chongqing Engineering Laboratory in Vascular Implants and the Public Experiment Center of State Bioindustrial Base (Chongqing).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcginty, Dr Sean and Pontrelli, Dr Giuseppe
• Authors: Yin, Y., Wang, J., Yang, M., Du, R., Pontrelli, G., McGinty, S., Wang, G., Yin, T., and Wang, Y.
• College/School: College of Science and Engineering > School of Engineering; College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Nanoscale
• Publisher: Royal Society of Chemistry
• ISSN: 2040-3364
• ISSN (Online): 2040-3372
• Published Online: 07 January 2020
• Copyright Holders: Copyright © 2020 The Royal Society of Chemistry
• First Published: First published in Nanoscale 12:2946-2960
• Publisher Policy: Reproduced in accordance with the publisher copyright policy