A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice
Tingting Jia,1,* Zhiguo Sun,1,* Ying Lu,1 Jie Gao,1 Hao Zou,1 Fangyuan Xie,2 Guoqing Zhang,2 Hao Xu,3 Duxin Sun,3 Yuan Yu,1 Yanqiang Zhong1 1Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University, 2Department of Pharmacy, Eastern Hepatobiliary Surgery Hosp...
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Dove Medical Press
2016
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oai:doaj.org-article:38564ced0b0d4d0cb5c9f9671018cc0d2021-12-02T05:04:23ZA dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice1178-2013https://doaj.org/article/38564ced0b0d4d0cb5c9f9671018cc0d2016-08-01T00:00:00Zhttps://www.dovepress.com/a-dual-brain-targeting-curcumin-loaded-polymersomes-ameliorated-cognit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tingting Jia,1,* Zhiguo Sun,1,* Ying Lu,1 Jie Gao,1 Hao Zou,1 Fangyuan Xie,2 Guoqing Zhang,2 Hao Xu,3 Duxin Sun,3 Yuan Yu,1 Yanqiang Zhong1 1Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University, 2Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of Pharmaceutical Sciences, School of Pharmacy, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Due to the impermeability of the blood–brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood–brain barrier permeability–surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics. Keywords: polymersomes, transferrin, Tet-1 peptide, Alzheimer’s diseaseJia TTSun ZGLu YGao JZou HXie FYZhang GQXu HSun DXYu YZhong YQDove Medical PressarticlepolymersomestransferrinTet-1 peptidebrain targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3765-3775 (2016) |
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polymersomes transferrin Tet-1 peptide brain targeting Medicine (General) R5-920 |
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polymersomes transferrin Tet-1 peptide brain targeting Medicine (General) R5-920 Jia TT Sun ZG Lu Y Gao J Zou H Xie FY Zhang GQ Xu H Sun DX Yu Y Zhong YQ A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| description |
Tingting Jia,1,* Zhiguo Sun,1,* Ying Lu,1 Jie Gao,1 Hao Zou,1 Fangyuan Xie,2 Guoqing Zhang,2 Hao Xu,3 Duxin Sun,3 Yuan Yu,1 Yanqiang Zhong1 1Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University, 2Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of Pharmaceutical Sciences, School of Pharmacy, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Due to the impermeability of the blood–brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood–brain barrier permeability–surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics. Keywords: polymersomes, transferrin, Tet-1 peptide, Alzheimer’s disease |
| format |
article |
| author |
Jia TT Sun ZG Lu Y Gao J Zou H Xie FY Zhang GQ Xu H Sun DX Yu Y Zhong YQ |
| author_facet |
Jia TT Sun ZG Lu Y Gao J Zou H Xie FY Zhang GQ Xu H Sun DX Yu Y Zhong YQ |
| author_sort |
Jia TT |
| title |
A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| title_short |
A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| title_full |
A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| title_fullStr |
A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| title_full_unstemmed |
A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| title_sort |
dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://doaj.org/article/38564ced0b0d4d0cb5c9f9671018cc0d |
| work_keys_str_mv |
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