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探討Pluronic和磷脂體的交互作用及其超音波控制釋放機制與對肝癌細胞...
~
國立高雄大學生物科技研究所
探討Pluronic和磷脂體的交互作用及其超音波控制釋放機制與對肝癌細胞HepG2的體外實驗 = Investigation of interactions between Pluronic and liposomes, and their controlled release by ultrasound to HepG2 cells in vitro
紀錄類型:
書目-語言資料,印刷品 : 單行本
並列題名:
Investigation of interactions between Pluronic and liposomes, and their controlled release by ultrasound to HepG2 cells in vitro
作者:
楊士毅,
其他團體作者:
國立高雄大學
出版地:
[高雄市]
出版者:
撰者;
出版年:
2010[民99]
面頁冊數:
151面圖,表 : 30公分;
標題:
HepG2
標題:
HepG2
電子資源:
http://handle.ncl.edu.tw/11296/ndltd/03008797137139656501
摘要註:
磷脂體為磷脂分子以脂雙層形式排列所構成之載體,經由靜脈注射進入循環系統後,將從高通透性的腫瘤微血管滲出而被動累積於腫瘤內,此即「促進性滲透與滯留效應」(enhanced permeability and retention effect, EPR effect),再藉由與細胞膜融合及胞飲作用進入細胞內釋出藥物,然而,此途徑之藥物釋放速率過慢而無法於短時間內提升局部藥物濃度至有效毒殺癌細胞的程度,故為了有效控制磷脂體釋放,具備不同釋放機制的磷脂體設計而出,主要可分為溫度敏感型、酸鹼值敏感型與超音波敏感型磷脂體。溫度敏感型磷脂體是利用局部高熱促進組織的外滲作用同時觸發磷脂體釋放藥物,缺點為局部高熱有其安全限度使磷脂體釋放速度受限;酸鹼敏感型磷脂體是利用其於核內體酸性環境下迅速降解之特性來觸發藥物釋放,缺點是受限於細胞攝取磷脂體的速率;超音波敏感型磷脂體則是利用超音波之空洞效應(cavitation)促使溶液中的氣體不斷聚集形成氣泡並崩解產生高速微噴流,衝擊細胞膜生成裂隙以提高磷脂體的藥物釋放速率,超音波具非侵入性、低成本、便利性高及可產生訊號等優點,極適合作為磷脂體的釋放機制,但磷脂體本身對超音波的感受性低,故本研究利用Pluronic高分子來提升磷脂體的超音波感受性。Pluronic為非離子型界面活性劑,是聚氧乙烯/聚氧丙烯型的三段式共聚高分子,結構式為(EO)m-(PO)n-(EO)m,兩端PEO鏈為親水性,中間PPO鏈為親油性,當Pluronic以聚氧丙烯鏈吸附至磷脂體表面後,可減弱脂雙層結構強度,提高磷脂體對超音波的感受性。研究中將探討超音波之強度、震盪時間與工作週期、Pluronic之濃度與種類、磷脂體粒徑與溫度對磷脂體釋放情形的影響及磷脂體與Pluronic間的交互作用,並利用包覆抗癌藥物5-氟尿嘧啶的Pluronic磷脂體對肝癌細胞HepG2進行體外超音波控制釋放實驗。 Liposomes are self-assembled by phospholipids and used as carriers. After liposomes are intravenously injected into the circulatory system, the high-permeability of vessels allow them to penetrate and passive accumulate in tumor, which called “enhanced permeability and retention effect”(EPR effect). Then liposomes would infuse with cell membrane or be uptaken by pinocytosis of cells releasing drugs. However, the drug releasing rate of this passway is not fast enough to raise local drug concentration up to toxic level in short time. In order to control the release of liposomes, thermo-sensitive, pH-sensitive and ultrasound-sensitive liposomes are designed. Extravasation and release of thermo-sensitive liposomes are enhanced by local hyperthermia, but limited by safety. pH-sensitive liposomes are degraded in acidic environment of endosomes, but the drug releasing rate is limited by pinocytosis. Ultrasound-sensitive liposomes release drugs by ultrasonic cavitation, which makes bubbles in solution aggregating, fusion and collapse. The micro-jet from the collapse of bubbles makes fissure on membranes and enhances the drug release. Ultrasound is non-invasive, low-cost, highly convenient and could deliver signals, but ultrasonic sensitivity of liposomes is low. In this study, Pluronic is used to enhance the ultrasonic responsivity of liposomes. Pluronic is non-ionic surfactant and triblock polymer composed of polyethylene and polypropylene. Both sides are hydrophilic PEO chains and the middle is hydrophobic PPO chain. When Pluronics adsorb on the surface of liposomes with its PEO chain, the strength of bilayer reduces and the ultrasonic responsivity of liposomes is enhanced. Moreover, ultrasonic power, insonation time and duty cycle, Pluronic concentration and type, liposome size and temperature also take into account about the liposomal release and the interactions between liposomes and Pluronics. 5-Fluorouracil loaded liposomes coating Pluronics are used to research in vitro controlled release by ultrasound on HepG2 cells.
探討Pluronic和磷脂體的交互作用及其超音波控制釋放機制與對肝癌細胞HepG2的體外實驗 = Investigation of interactions between Pluronic and liposomes, and their controlled release by ultrasound to HepG2 cells in vitro
楊, 士毅
探討Pluronic和磷脂體的交互作用及其超音波控制釋放機制與對肝癌細胞HepG2的體外實驗
= Investigation of interactions between Pluronic and liposomes, and their controlled release by ultrasound to HepG2 cells in vitro / 楊士毅撰 - [高雄市] : 撰者, 2010[民99]. - 151面 ; 圖,表 ; 30公分.
參考書目:面120-125.
HepG2HepG2
探討Pluronic和磷脂體的交互作用及其超音波控制釋放機制與對肝癌細胞HepG2的體外實驗 = Investigation of interactions between Pluronic and liposomes, and their controlled release by ultrasound to HepG2 cells in vitro
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磷脂體為磷脂分子以脂雙層形式排列所構成之載體,經由靜脈注射進入循環系統後,將從高通透性的腫瘤微血管滲出而被動累積於腫瘤內,此即「促進性滲透與滯留效應」(enhanced permeability and retention effect, EPR effect),再藉由與細胞膜融合及胞飲作用進入細胞內釋出藥物,然而,此途徑之藥物釋放速率過慢而無法於短時間內提升局部藥物濃度至有效毒殺癌細胞的程度,故為了有效控制磷脂體釋放,具備不同釋放機制的磷脂體設計而出,主要可分為溫度敏感型、酸鹼值敏感型與超音波敏感型磷脂體。溫度敏感型磷脂體是利用局部高熱促進組織的外滲作用同時觸發磷脂體釋放藥物,缺點為局部高熱有其安全限度使磷脂體釋放速度受限;酸鹼敏感型磷脂體是利用其於核內體酸性環境下迅速降解之特性來觸發藥物釋放,缺點是受限於細胞攝取磷脂體的速率;超音波敏感型磷脂體則是利用超音波之空洞效應(cavitation)促使溶液中的氣體不斷聚集形成氣泡並崩解產生高速微噴流,衝擊細胞膜生成裂隙以提高磷脂體的藥物釋放速率,超音波具非侵入性、低成本、便利性高及可產生訊號等優點,極適合作為磷脂體的釋放機制,但磷脂體本身對超音波的感受性低,故本研究利用Pluronic高分子來提升磷脂體的超音波感受性。Pluronic為非離子型界面活性劑,是聚氧乙烯/聚氧丙烯型的三段式共聚高分子,結構式為(EO)m-(PO)n-(EO)m,兩端PEO鏈為親水性,中間PPO鏈為親油性,當Pluronic以聚氧丙烯鏈吸附至磷脂體表面後,可減弱脂雙層結構強度,提高磷脂體對超音波的感受性。研究中將探討超音波之強度、震盪時間與工作週期、Pluronic之濃度與種類、磷脂體粒徑與溫度對磷脂體釋放情形的影響及磷脂體與Pluronic間的交互作用,並利用包覆抗癌藥物5-氟尿嘧啶的Pluronic磷脂體對肝癌細胞HepG2進行體外超音波控制釋放實驗。 Liposomes are self-assembled by phospholipids and used as carriers. After liposomes are intravenously injected into the circulatory system, the high-permeability of vessels allow them to penetrate and passive accumulate in tumor, which called “enhanced permeability and retention effect”(EPR effect). Then liposomes would infuse with cell membrane or be uptaken by pinocytosis of cells releasing drugs. However, the drug releasing rate of this passway is not fast enough to raise local drug concentration up to toxic level in short time. In order to control the release of liposomes, thermo-sensitive, pH-sensitive and ultrasound-sensitive liposomes are designed. Extravasation and release of thermo-sensitive liposomes are enhanced by local hyperthermia, but limited by safety. pH-sensitive liposomes are degraded in acidic environment of endosomes, but the drug releasing rate is limited by pinocytosis. Ultrasound-sensitive liposomes release drugs by ultrasonic cavitation, which makes bubbles in solution aggregating, fusion and collapse. The micro-jet from the collapse of bubbles makes fissure on membranes and enhances the drug release. Ultrasound is non-invasive, low-cost, highly convenient and could deliver signals, but ultrasonic sensitivity of liposomes is low. In this study, Pluronic is used to enhance the ultrasonic responsivity of liposomes. Pluronic is non-ionic surfactant and triblock polymer composed of polyethylene and polypropylene. Both sides are hydrophilic PEO chains and the middle is hydrophobic PPO chain. When Pluronics adsorb on the surface of liposomes with its PEO chain, the strength of bilayer reduces and the ultrasonic responsivity of liposomes is enhanced. Moreover, ultrasonic power, insonation time and duty cycle, Pluronic concentration and type, liposome size and temperature also take into account about the liposomal release and the interactions between liposomes and Pluronics. 5-Fluorouracil loaded liposomes coating Pluronics are used to research in vitro controlled release by ultrasound on HepG2 cells.
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