Taipei Medical University Institutional Repository:Item 987654321/54326
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    Title: 硫醇與胺基雙官能基修飾之矽奈米粒的製備與性質研究:應用於反譯寡核苷酸之遞送
    Preparation and Characterization of Thiol and Amine Bifunctionalized Silica Nanoparticles: Application to Delivery of Antisense Oligonucleotides
    Authors: 王思元
    Wang, Su-Yuan
    Keywords: 矽奈米粒;反譯寡核苷;;fluorescence quenching;藥物遞送;MTS assay;silica nanoparticle;antisense oligonucleotide;fluorescence quenching;drug delivery;MTS assay
    Date: 2013-06-28
    Issue Date: 2018-11-20 12:05:48 (UTC+8)
    Abstract: 矽奈米粒 (silica nanoparticles; SiNPs) 是近年來藥物製劑上的研究趨勢,目前相關研究已證實SiNPs具生物相容性 (biocompatibility)。傳統製備SiNPs的方法稱作Stober method,此法係利用有機矽酸衍生物在鹼性的酒精溶液中,經過水解及縮合反應後而合成奈米粒子。SiNPs的粒子表面可進行有機官能基的修飾,使其具多功能的用途。本實驗之目的為: (1) 發展出簡便合成SiNPs之方法,使SiNPs帶有硫醇 (SH) 和胺基 (NH2) 兩種官能性基團;(2) 探討SiNPs承載反譯寡核苷酸 (ODN) 之吸附及釋放特性;(3) 探討SiNP-ODN製劑之細胞攝入 (cellular uptake) 及細胞毒性 (cytotoxicity)。本研究使用兩種矽源 (silica source): 3-aminopropyltrimethoxysilane (APTMS) 和3-mercaptopropyl trimethoxysilane (MPTMS) 進行SiNPs之製備,將不同比例的矽源在酸性有機溶劑中反應,經過相轉移後,在水相中析出成粒子。為了能進一步瞭解此系統,我們嘗試改變不同的實驗條件。
    實驗結果顯示,影響SiNPs生成的主要因素為:矽烷組成比例、矽烷總濃度、反應時間、注射體積和反應溫度。當APTMS佔組成的1-25 %,可生成200 - 300 nm穩定大小的SiNPs;SiNPs上硫醇的濃度是隨著參與反應的MPTMS比例越高而增加;各比例SiNPs的表面所帶電荷皆大於+ 30 mV,電荷是隨著參與反應的APTMS比例越高而提高; SiNPs的分子鍵結 (Si) 是以約1:1的T2和T3形成網狀致密的圓球體構型。細胞試驗結果顯示,SiNPs能有效遞送FITC-G3139 (FITC螢光標記之ODN) 進入細胞,且可提升doxorubicin對血液腫瘤細胞K562和CCRF-CEM的抑制生長作用。
    結論:本研究發展出新穎、簡便的方法,利用ouzo effect製備表面具SH與NH2雙官能基修飾的矽奈米粒,所製備的SiNPs表面帶正電荷且具有良好的膠體安定性 (colloid stability),預期此法所製備的SiNPs具有廣泛的應用性。
    Description: 碩士
    委員-劉英麟
    委員-何秀娥
    委員-陳建中
    共同指導教授-胡德民
    指導教授-邱士娟
    Data Type: thesis
    Appears in Collections:[School of Pharmacy] Dissertation/Thesis

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