以氫氧基磷灰石作為藥物載體應用於預防阿茲海默症之研究

Abstract

阿茲海默症是現代老年化社會普及的一種神經退化疾病，會嚴重影響患者的日常生活以及為身邊的人帶來諸多不便。目前阿茲海默症無法完全根治，只能透過藥物改善或是減緩病情的惡化。預防醫學對於老年化社會是一項重要的議題，也是目前醫學上的重點發展。因此，希望藉由預防注射來代替口服的給藥方式，讓患者免於每日服藥的不便性，也減輕照護者的負擔。 本研究以氫氧基磷灰石/多奈哌齊 (donepezil) 材料作為實驗主要的藥物載體，並探討氫氧基磷灰石作為多奈哌齊載體材料之特性及載藥量。本研究主要分為材料分析、載藥量分析、藥物釋放分析、體外細胞實驗與初步之動物實驗。 透過 XRD、FTIR、SEM 觀察氫氧基磷灰石/多奈哌齊之分析，證實多奈哌齊確實被氫氧基磷灰石所包覆。以 TGA 分析得到其載藥量約為 12 %。藥物釋放測試顯示氫氧基磷灰石/多奈哌齊於酸性環境下多奈哌齊很快就被大量釋放出來。藉由體外細胞試驗 WST-1 與 LDH ,結果顯示氫氧基磷灰石/多奈哌齊並不會對細胞的增生或存活造成影響，同時也不會對細胞造成毒性。 由研究結果顯示，氫氧基磷灰石/多奈哌齊對於阿茲海默症的預防具有潛在的臨床運用價值。

Alzheimer’s disease (AD) is the most common type of neurodegenerative disease in aging society, which will reducing life quality of patients, and inconvenience to the caregivers. However, Alzheimer’s disease is currently that is no drug can successfully treat it. Current approaches focus on slowly or delay the symptoms of Alzheimer’s disease. Hence, researchers hope to develop therapies that the actual underlying cause of the disease can be prevented. The purpose of study is to develop hydroxyapatite/donepezil which could carry drugs. The material synthesis, drug loading test, drug release test, in vitro study and in vivo study were evaluated. In material synthesis study, donepezil is indeed into hydroxyapatite was confirmed by XRD analysis, FTIR, and SEM observations. TGA analysis showed the drug loading of hydroxyapatite/donepezil is about 12 %. The drug release tests showed hydroxyapatite/donepezil a great number of donepezil release in the acidic environment in a short time. In in vitro study, WST-1 test showed there is no negative effect on cell viability and cell proliferation. LDH test showed no cytotoxicity on cell. The results suggest that hydroxyapatite/donepezil would be a potential candidate for prevention Alzheimer’s disease.