研究生: |
張家錞 Chia-Chun Chang |
---|---|
論文名稱: |
適合製備奈米顆粒之聚縮酮高分子 及研究其抗發炎特性 Preparation of Nanoparticles with the Novel Polyketal Polymers and Evaluation of Their Anti-inflammatory Properties |
指導教授: |
高震宇
Chen-Yu Kao |
口試委員: |
李曉屏
Shiao-Pieng Lee 鄭智嘉 Chih-Chia Cheng |
學位類別: |
碩士 Master |
系所名稱: |
應用科技學院 - 醫學工程研究所 Graduate Institute of Biomedical Engineering |
論文出版年: | 2018 |
畢業學年度: | 106 |
語文別: | 中文 |
論文頁數: | 136 |
中文關鍵詞: | 白楊素 、聚縮酮 、抗發炎 、奈米顆粒 |
外文關鍵詞: | Chrysin, PCADK, Anti-inflammatory, nanoparticles |
相關次數: | 點閱:245 下載:1 |
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白楊素( Chrysin ),被認為與許多疾病的生理機制及訊息傳遞路徑相關,但其呈疏水性且溶解度差與懸浮性不佳等特性,使其臨床應用受限。而聚縮酮( Polyketal ) 已用於包覆親、疏水性與蛋白質藥物運用於心血管、急性發炎與癌症等疾病之功能。故本研究將Chrysin與1,4-Cyclohexanedimethanol ( CDM )及2,2-Diethoxypropane ( DEP )合成為具抗發炎功效之聚縮酮( Polyketal )聚合物—PCADK-Chrysin,藉Chrysin增強聚縮酮抗發炎之功效。
第一階段,本實驗以不同比例之Chrysin與CDM合成數種新穎聚縮酮,其中Chrysin含量無法計算,分子量約為5600-12500 Dalton,裂解溫度120-195°C,且發現略減CDM之比例可提升分子量,其中PCADK-Chry.15%( CDM:DEP = 0.85:1 )組別分子量及裂解溫度較高。因此第二階段合成PCADK-CDM聚合物藉調整CDM及DEP比例,期以得到較高分子量之PCADK-CDM聚合物,藉此聚合物包覆Chrysin提高Chrysin含量,模擬PCADK-Chrysin NPs分析其抗發炎能力與細胞毒性。
第二階段,成功合成PCADK-CDM聚合物,其分子量及裂解溫度特性與PCADK-Chrysin趨勢相同,PCADK-CDM85%( CDM:DEP = 0.85:1 )組別分子量及裂解溫度較高,製備出之顆粒型態最完整,包埋率約為59.28%。
細胞實驗中,PCADK-CDM NPs 具有強烈奈米尺度毒性,Chrysin-PCADK-CDM NPs與純藥皆顯示未能抑制LPS所引起NO之釋放。
Chrysin, a natural anti-inflammatory compound, exhibits many beneficial effects. However, the hydrophobicity, low-solubility and poor-suspension properties of Chrysin have limited its clinical application.
In this study, we tried to solve the above problem by the following two methods: first, synthesis of a series of polymers containing Chrysin, and second, encapsulation of Chrysin into the polyketal nanoparticles.
In the first method, we synthesized several novel polyketal polymers based on different ratios of Chrysin and CDM. The results showed that the contents of Chrysin in these polymers can’t be calculated. The molecular weight of PCADK-Chrysin polymers ranges between 5600 and 12500 Dalton. The decomposition-temperature of PCADK-Chrysin were range between 120-195°C. Among these polymers, PCADK-Chrysin.15% ( CDM:DEP = 0.85:1 ) exhibit the highest decomposition-temperature and molecular weight.
In the second method, we synthesized PCADK-CDM with the same characteristic of PCADK-Chrysin. PCADK-CDM85%( CDM:DEP = 0.85:1 ) has the highest decomposition-temperature and molecular weight that can obtain the most completed nanoparticles. These PCADK-CDM NPs were used to encapsulate Chrysin, and the encapsulation efficiency is 59.28%.
However, the results in our in vitro test showed that PCADK-CDM NPs exhibited high cytotoxicity of nano-scale. Both Chrysin-PCADK-CDM NPs and the pure drug could not inhibit LPS induced NO production.
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