Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system
Dan Zou,1 Wei Wang,1 Daoxi Lei,1 Ying Yin,1 Peng Ren,1 Jinju Chen,2 Tieying Yin,1 Bochu Wang,1 Guixue Wang,1 Yazhou Wang1 1Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China...
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Dove Medical Press
2017
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oai:doaj.org-article:50d3dd603fa047b2854cc9622491d6562021-12-02T05:04:24ZPenetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system1178-2013https://doaj.org/article/50d3dd603fa047b2854cc9622491d6562017-07-01T00:00:00Zhttps://www.dovepress.com/penetration-of-blood-brain-barrier-and-antitumor-activity-and-nerve-re-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dan Zou,1 Wei Wang,1 Daoxi Lei,1 Ying Yin,1 Peng Ren,1 Jinju Chen,2 Tieying Yin,1 Bochu Wang,1 Guixue Wang,1 Yazhou Wang1 1Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China; 2School of Mechanical and System Engineering, Newcastle University, Newcastle Upon Tyne, UK 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. Keywords: blood–brain barrier, GM1, nanovesicles, doxorubicin, glioma, zebrafishZou DWang WLei DYin YRen PChen JYin TWang BWang GWang YDove Medical Pressarticleblood-brain barrierGM1micellesDoxorubicingliomazebrafishMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4879-4889 (2017) |
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blood-brain barrier GM1 micelles Doxorubicin glioma zebrafish Medicine (General) R5-920 |
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blood-brain barrier GM1 micelles Doxorubicin glioma zebrafish Medicine (General) R5-920 Zou D Wang W Lei D Yin Y Ren P Chen J Yin T Wang B Wang G Wang Y Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| description |
Dan Zou,1 Wei Wang,1 Daoxi Lei,1 Ying Yin,1 Peng Ren,1 Jinju Chen,2 Tieying Yin,1 Bochu Wang,1 Guixue Wang,1 Yazhou Wang1 1Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China; 2School of Mechanical and System Engineering, Newcastle University, Newcastle Upon Tyne, UK 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. Keywords: blood–brain barrier, GM1, nanovesicles, doxorubicin, glioma, zebrafish |
| format |
article |
| author |
Zou D Wang W Lei D Yin Y Ren P Chen J Yin T Wang B Wang G Wang Y |
| author_facet |
Zou D Wang W Lei D Yin Y Ren P Chen J Yin T Wang B Wang G Wang Y |
| author_sort |
Zou D |
| title |
Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| title_short |
Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| title_full |
Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| title_fullStr |
Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| title_full_unstemmed |
Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| title_sort |
penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system |
| publisher |
Dove Medical Press |
| publishDate |
2017 |
| url |
https://doaj.org/article/50d3dd603fa047b2854cc9622491d656 |
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