研究生: |
沈芷薇 Shen, Chih-Wei |
---|---|
論文名稱: |
以mPEG-PLCL自組裝形成微胞作為包覆阿黴素載體之研究 Development of mPEG-PLCL micelles for doxorubicin delivery |
指導教授: |
朱一民
Chu, I-Ming |
口試委員: |
蔡德豪
林世傑 |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2019 |
畢業學年度: | 107 |
語文別: | 中文 |
論文頁數: | 54 |
中文關鍵詞: | 奈米微胞 、阿黴素 、聚酯類高分子 |
外文關鍵詞: | doxorubicin, mPEG-PLCL, nanoparticle |
相關次數: | 點閱:1 下載:0 |
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部分聚酯類高分子為具有良好生物相容性且可降解之材料,做為藥物載體時具有可控制釋放的性質,故目前在醫藥領域中受到重視。本研究利用包含聚酯類的高分子且帶有兩親性的團聯共聚物,在水相環境中可以自組裝形成疏水在內而親水在外的微胞,利用此核殼結構的微胞來包覆藥物,可以達到控制釋放並提升藥物療效的目的。
本研究利用methoxy poly(ethylene glycol)作為起始劑,加入D, L-lactide及caprolactone進行開環聚合反應,合成出不同鏈段長短的mPEG-PLCL兩親性團聯共聚物。利用1H-NMR、FTIR與GPC確定高分子的結構與分子量,並測量臨界微胞濃度與表面性質,實驗結果顯示所合成的高分子在低濃度下即可形成微胞。而粒徑測量結果可發現,當高分子親水鏈段增長時,微胞粒徑則隨之上升,而疏水鏈段增長時,微胞粒徑則下降。在TEM下可觀察到微胞呈現球狀且分散性良好,沒有明顯聚集的現象。
阿黴素(Doxorubicin)為目前臨床應用的抗癌藥物,本研究選用阿黴素做為包覆的藥物,並利用不同製備方法來製成微胞。製備方法可分為薄膜分散法、超音波分散法與溶劑分散法,並探討不同製備方法以及不同高分子組成在微胞性質與包覆程度之差異,以找出最適合的製程。結果顯示薄膜分散法的包覆量較高,約為2.1 wt%。微胞粒徑為135 nm左右,並可穩定維持兩天以上。體外藥物釋放結果顯示,包藥後的微胞能改善藥物突釋現象,並且在24小時後依然持續釋放藥物。由細胞實驗可發現所合成高分子的生物相容性良好,且包藥後的微胞有良好毒殺癌細胞的能力。
由以上結果顯示,mPEG-PLCL兩親性團聯共聚物確實可做為包覆藥物之材料,且微胞粒徑在50-200 nm時有助於腫瘤組織的高滲透長滯留效應,讓微胞集中累積在腫瘤內,使此微胞具有良好的發展潛力。
Certain polyesters are well-known for their good biocompatibility and biodegradability, so plenty of studies have been conducted on using polyesters for biomedical applications. And owing to the self-assembly behavior of amphiphilic block copolymers, micellar structures are formed in aqueous system with hydrophobic segments as core and hydrophilic segments as shell. By the encapsulation of hydrophobic drugs and the proper-designed function of controlled release, the drug loaded micelles could be used as drug carriers to improve the therapeutic effect of drugs.
In this study, methoxy poly(ethylene glycol)-co-poly(D, L-lactide-co-ε-caprolactone) (mPEG-PLCL) was studied for drug delivery. By changing the ratio between hydrophilic and hydrophobic blocks, mPEG-PLCL micelles were optimized to carry doxorubicin (DOX) with higher loading content and stability in aqueous system. Meanwhile, different preparation methods were compared, including film dispersion method, ultrasonic dispersion method and solvent dispersion method. Here, mPEG-PLCL polymers were analyzed by 1H-NMR, GPC and FTIR to characterize their molecular structures and molecular weights. Their physicochemical properties, morphology, stability and loading capacity were also measured. The size of these micelles were around 50-200 nm, which were suitable for EPR effect at tumor sites. DOX-loaded NPs presented a sustained release behavior with less burst release at the beginning. In vitro cytotoxicity test showed that DOX-loaded NPs had excellent antitumor effect. Therefore, after further adjustments, these DOX loaded micelles could become promising candidates for cancer therapy.
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