2018 Fiscal Year Research-status Report
Developing brain-penetrating anti-inflammatory nano-medicines to treat neurodegenerative diseases
| Project/Area Number |
18K14100
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
ゴンザレスカーター ダニエル 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (80800903)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Nanomicelle / Protein loading / CD200 protein / Brain inflammation |
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| Outline of Annual Research Achievements |
We have successfully conjugated the anti-inflammatory protein CD200 onto azide-decorated polymeric nanomicelles (PNM) specifically through a Click-chemistry reaction between DBCO (linked to the protein) and the azide groups. Characterization of the protein-loaded PNM indicates a slight increase in diameter with retention of a low polydispersity index, indicating lack of particle aggregates which might affect the biological activity of the protein or brain penetration of the PNM. Furthermore, fluorescence correlation spectroscopy indicates 1.15 protein loading per PNM. Furthermore, the CD200-loaded PNM are able to reduce brain inflammation, as evidenced by a reduction in nitric oxide and reactive oxygen species production (in vitro) by inflammed microglial cells following CD200-PNM treatment, demonstrating loading onto PNM does not affect the biological activity of CD200. In summary, we have successfully created protein-loaded PNM with anti-inflammatory potential which we will next modify with glucose decoration to achieve brain penetration.
In addition, we have data examining the effect of protein loading (Fab' antibody fragments as control proteins) on the ability of glucose decorated micelles to penetrate the brain in vivo.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
The azide decorated polymeric nano micelles (PNM) have been successfully loaded with an anti-inflammatory protein (CD200) which has been shown to retain its biological activity to reduce brain inflammation in vitro. However, the synthesis of the glucose-decorated PNM has been troublesome, therefore the ability of CD200-loaded proteins to enter the brain has not been able to be examined yet.
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| Strategy for Future Research Activity |
The synthesis of the glucose polymer will be optimised and standardised to ensure reliable synthesis for polymeric nanomicelle synthesis. After successful synthesis, the composition of the anti-inflammatory CD200-loaded polymeric nano micelles will be modified to include glucose decoration. This will allow for the examination of brain penetration, reduction of brain inflammation in vivo, and therapeutic effects on animal models of Alzheimer's disease.
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| Causes of Carryover |
Glucose-micelle experiments delayed until next fiscal year
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Research Products
(2 results)
