標題: 酸鹼敏感型幾丁聚醣-甲氧基苄腈奈米殼核粒子應用於藥物輸送,細胞內顯影與酸鹼環境監測
pH-Sensitive Chitosan-Pyranine Core-Shell Nanoparticles for Drug Delivery, Intracellular Lightening and pH Monitoring
作者: 洪維陽
劉典謨
Liu, Dean-Mo
材料科學與工程學系所
關鍵字: 兩性幾丁聚醣;甲氧基苄腈;細胞顯影;酸鹼性量測;藥物釋放;Carboxymethy-hexanoyl chitosan;pyranine;cell-imaging;pH determination;drug release
公開日期: 2011
摘要: 本實驗中將兩性幾丁聚醣CHC與螢光染劑甲氧基苄腈Pyranine,,運用層接層(Layer-By-Layer)技術,藉由靜電吸附的方式將螢光染劑甲氧基苄腈吸附在自組裝奈米載體CHC之表面上,成功製備出一種多功能藥物輸送奈米載體(CHC-PY)。其形成的層階層奈米載體之外觀形貌由掃描式電子顯微鏡(SEM)與穿透式電子顯微鏡(TEM)觀察;此外粒徑分析由SEM、DLS偵測,發現其層階層形成之粒徑與吸附甲氧基苄腈的濃度有關。在奈米膠囊帶電性部分也發現吸附甲氧基苄腈之濃度越高,其帶電性由正電減少至接近電中性,進而證實甲氧基苄腈確實覆蓋於CHC表面上形成殼核結構。此甲氧基苄腈殼層可以形成一層物理屏障來保護藥物與延長藥物釋放速率。在藥物釋放的探討上,採用疏水性抗癌藥物CPT作為模擬藥物,可以發現此奈米載體具有非常好的藥物包覆率(>95%),經由不同吸附比例來調控其奈米載體之藥物釋放速率。我們證明此層階層奈米載體比CHC奈米載體能夠有效的遲緩藥物釋放速率。最後,此層階層奈米載體在人體正常細胞(IEC-6)與癌細胞(MCF-7、A-549)表現出非常好的細胞相容性,以及直接的細胞內顯影。此甲氧基苄腈殼層並具有提供準確和穩定的細胞內pH值測定能力,讓此多功能載體在醫學上更具有利用價值。
In this study, we successfully manufactured a new multifunctional drug delivery nanocapsule which was prepared through the electrostatic interactions between the CHC nanoparticles and pyranine, which formed a layer-by-layer (LBL) self-assembly nanocapsule (CHC-PY). Structural morphology of the pyranine-coated CHC nanoparticles was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM). And the mean size of CHC-PY was characterized by SEM and dynamic light scatter (DLS) measurements which demonstrated a pyranine concentration-dependent assembly size. The measurement of zeta-potential indicated that the charge of nanoparticles was reduced to be close to neutral and the size of increase after coating pyranine. The addition of pyranine shell would serve as a physical barrier to protect the drug and prolong drug release. The CHC-PY nanocapsule showed excellent encapsulation efficiency greater than 96% for an anti-cancer, hydrophobic molecule, (S)-(+)-Camptothecin (CPT). Additional study of the CHC to PY ratio on the nanoparticles and drug release rate revealed that CHC to PY ratio could manipulate the rate of drug release. We proved that CHC-PY nanocapsule had significantly enhanced CPT retention rate when compared to CHC-only nanocapsule. Finally, the CHC-PY nanocapsule also demonstrated outstanding biocompatibility in normal cell (IEC-6) and cancer cell (MCF-7 and A-549), as well as direct cellular-imaging.. The experimental results also showed that the CHC-PY to provide accurate and stable intracellular pH determination. To the above results suggest a promising vehicle for medical application.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT079918535
http://hdl.handle.net/11536/49630
顯示於類別:畢業論文