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標題: | 以環境敏感型高分子:幾丁聚醣與聚(氮-異丙基丙烯醯胺)製備奈米顆粒於藥物釋放的研究 Studies on Drug Release of Nanoparticles Synthesized with Stimuli-Responsive Polymers: Chitosan and PNIPAAm |
作者: | Cheng-Fan Wang 王晨帆 |
指導教授: | 邱文英 |
關鍵字: | 幾丁聚醣,自組裝,氮-異丙基丙烯醯胺,溫度敏感,藥物控制釋放, stimuli-responsive,chitosan,self-assembly,N-isopropylacrylamide,drug controlled release, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 本研究是利用環境敏感型高分子製備奈米顆粒並應用於藥物釋放。系統架構是利用酸鹼敏感型天然高分子-幾丁聚醣,在醋酸水溶液中進行自組裝,形成幾丁聚醣/醋酸錯合微胞。接續在微胞中加入氮-異丙基丙烯醯胺單體,以過硫酸鉀在高溫下起始反應,由於生成的聚(氮-異丙基丙烯醯胺)為溫度敏感型高分子,當反應溫度高於其最低臨界溶解溫度時,高分子鏈產生疏水性而縮進微胞中,最後交聯外層幾丁聚醣,完成[幾丁聚醣/醋酸]-聚(氮-異丙基丙烯醯胺)奈米顆粒製備。
實驗的第一部分討論幾丁聚醣/醋酸微胞的成形條件、形態觀察與粒徑分析。首先使用螢光光譜儀並以芘做為疏水探針,測量幾丁聚醣/醋酸之臨界微胞濃度,討論醋酸濃度與氮-異丙基丙烯醯胺單體,對於臨界微胞濃度的影響。接續使用穿透式電子顯微鏡與動態粒徑分析儀研究微胞的形態與粒徑。 實驗的第二部分為[幾丁聚醣/醋酸]-聚(氮-異丙基丙烯醯胺)奈米顆粒的製程研究。藉由調控單體進料量、交聯劑進料量、交聯溫度、反應溫度等參數討論對於顆粒形態、粒徑、界面電位的影響。顆粒溫感性質的測試是使用紫外光-可見光分光光譜儀,量測該顆粒之最低臨界溶解溫度;並利用動態粒徑分析儀,計算顆粒在升溫前後粒徑的收縮比率,並測試是否具有溫感可逆性。 實驗最後的部分為[幾丁聚醣/醋酸]-聚(氮-異丙基丙烯醯胺)奈米顆粒在藥物釋放的應用。模擬藥物選用鹽酸四環素,控制載藥環境進行包覆96小時,接續以離心的方式分離含藥顆粒,並透過上清液的未包覆藥物量推算藥物於顆粒含量及藥物包覆效率,同時討論初始載藥量對於包覆的影響。將含藥顆粒分散在不同環境(酸鹼值、溫度、鹽類濃度、酵素、自由基)的生理食鹽水中,探討各個變因對於累積釋放比率的影響,藉以了解顆粒對於藥物控制釋放的能力。 In this research, the stimuli-responsive polymers: chitosan(CS) and poly(N-isopropylacrylamide)(PNIPAAm) were used to synthesize the nanoparticles as a drug carrier. The amount of pH-sensitive polymer, chitosan, was adjusted to a proper molar ratio with acetic acid(HAc) to form CS/HAc micelles by self-assembly. Next, NIPAAm was introduced into the system and initialized by potassium persulfate(KPS) at high temperature which was higher than Lower Critical Concentration Temperature(LCST) of PNIPAAm; therefore, PNIPAAm polymer chain would become hydrophobic and shrink into micelles. The [CS/HAc]-PNIPAAm particles were eventually completed by cross-linking the the out-layer chitosan. The first part of this research was focused on the formation conditions of CS/HAc micelles, including the measurements of Critical Micellization Concentration(CMC), morphologies, and size distribution. CMC was measured by fluorescence spectrometer and pyrene was used as a hydrophobic probe. The effect of the concentration of acetic acid and presence of NIPAAm were studied. The observation of morphologies and size distribution were obtained with transmission electron microscopy(TEM) and dynamic light scattering(DLS), respectively. The second part was the synthesis of [CS/HAc]-PNIPAAm nanoparticle. The morphology, particle size distribution, and zeta-potential of the nanoparticles were discussed by manipulate several parameters such as concentration of NIPAAm and cross-linking agent, cross-linking temperature, and polymerization temperature. The thermo-sensitivity and LCST of particles were tested by UV-Vis spectrophotometer. Dynamic light scattering technique was also applied to examine the particle size-reversible ability. Finally, Doxycycline Hyclate was chosen as stimuli-drug and the drug-loaded particles were prepared under stable environmental conditions. After loading drug for 96hrs, the drug-loaded particles and the rest of stimuli-drug solution were separated via centrifugation process. The drug-loading content and the encapsulation efficiency were calculated via measuring the drug content in the upper phase of centrifugate. Furthermore, effect of initial drug-loading concentration on the encapsulation efficiency was discussed. Drug-loaded particles were dispersed in normal saline which was controlled in different conditions such as temperature, pH, concentration of salt, and the presence of enzyme and free radical. The release properties of drug-loaded particles in aforementioned conditions were studied. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25729 |
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顯示於系所單位: | 高分子科學與工程學研究所 |
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