| Summary: | 碩士 === 國立臺灣大學 === 醫學工程學研究所 === 107 === The World Alzheimer’s report estimated that, in 2015, a new dementia case was diagnosed every 3 seconds and total dementia cases will increase to 131.5 million by 2050. The healthcare cost of dementia worldwide will be 10 trillion. It has been a serious problem that we cannot ignore anymore. Dementia is 60-80 percent caused by Alzheimer (AD). AD is a neurodegenerative disorder of the central nervous system. It will cause cognitive and memory loss. As the result, lots of researches focus on therapy of Alzheimer. However, current therapies just improve cognition but doesn’t prevent neurodegeneration and regenerate neuron which has been degenerative. In other words, there is not a therapy that cure the Alzheimer.
In this research, we based on Amyloid-β (Aβ) hypothesis which indicates Alzheimer is caused by abnormal Aβ accumulation. Aβ will cause oxidative stress, inflammation and neuron dysfunction. Curcumin is a kind of natural extract which has great anti-oxidation and anti-inflammatory ability. Lots of researches showed that curcumin could inhibit Aβ aggregation and disaggregation of Aβ plague. Therefore, we used curcumin as multitarget therapy. However, curcumin can’t be absorbed and will degrade easily. To improve bioavailability, we synthesized PLGA-PEG-PLGA copolymer to prepare a drug delivery system. We used WST-1 assay to prove this copolymer had great biocompatibility. The polymer solution could carry curcumin to improve its water solubility and avoid degradation. In addition, the drug carrier could transform to hydrogel in body temperature and released curcumin until 25 days.
Curcumin-load PLGA-PEG-PLGA drug carrier (PGC) showed great result to reduce ROS synthesis in N2a cell and modulate inflammation. PGC also reduced cell-toxicity which caused by Amyloid-β oligomer. It performed excellent properties to protect neuro cell from degradation. By aluminum-induced Alzheimer animal model, we proved PGC could prevent wistar rat from neurodegeneration and memory declining.
We estimated that curcumin would inhibit Aβ aggregation and reduce oxidative stress during drug carrier release curcumin. In this research, we expected to develop a drug formulation to prevent Alzheimer up to 20 days.
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