本文選題：靜電層層自組裝 + 人工晶狀體�。� 參考：《浙江大學(xué)》2016年博士論文

【摘要】：目的：利用靜電層層自組裝法在人工晶狀體上修飾指數(shù)增長型載藥多層膜,并探索改性后的人工晶狀體其理化性質(zhì)、光學(xué)及力學(xué)性質(zhì)、體外細(xì)胞毒性以及殺菌性能。方法：利用次大氣等離子體技術(shù)結(jié)合靜電層層自組裝技術(shù),以妥布霉素和阿米卡星作為裝載藥物,在人工晶狀體表面組裝聚乙酰亞胺-(透明質(zhì)酸-聚賴氨酸/妥布霉素或阿米卡星)。-透明質(zhì)酸多層膜。利用接觸角測量檢測其親疏水性能。利用石英晶體微天平(QCM)全程模擬組裝過程,檢測自組裝膜的質(zhì)量、厚度及粘彈性能隨層數(shù)增加的變化,并驗(yàn)證指數(shù)模式增長。通過場發(fā)射掃描電鏡和原子力顯微鏡對改性后的人工晶狀體進(jìn)行表面形貌檢測,并計(jì)算表面粗糙度。利用X-射線光電子能譜對改性后的人工晶狀體進(jìn)行表面元素構(gòu)成分析,驗(yàn)證組裝過程的成功性。應(yīng)用SFDA關(guān)于IOL質(zhì)量檢測的國家標(biāo)準(zhǔn)(YY-0290)對改性后IOL進(jìn)行相關(guān)測試,包括像質(zhì)、光焦度、光譜透過率和動態(tài)疲勞耐久性等。將改性后人工晶狀體浸泡的細(xì)胞培養(yǎng)液與人晶狀體上皮細(xì)胞及人視網(wǎng)膜色素上皮細(xì)胞共同培養(yǎng),并用CCK-8實(shí)驗(yàn)檢測對這種兩種細(xì)胞的毒性作用。將改性后的人工晶狀體與表皮葡萄球菌共同培養(yǎng),通過熒光染料試劑盒在熒光顯微鏡下觀察活細(xì)菌與死細(xì)菌數(shù)量,檢測IOL的體外殺菌效果。結(jié)果：通過接觸角測定,改性后的IOL親水性大幅度提高。通過QCM模擬組裝過程,證實(shí)了組裝的成功性,且通過改進(jìn)組裝體系條件,IOL表面物質(zhì)的質(zhì)量與厚度隨層數(shù)增加呈指數(shù)增長模式,大大提高了改性效率和載藥量。場發(fā)射掃描電鏡和原子力顯微鏡顯示改性后IOL表面形貌和粗糙度無明顯改變。XPS顯示表面元素成分變化是組裝成功的表現(xiàn)。對改性后IOL進(jìn)行光焦度、像質(zhì)、光譜透過率和動態(tài)疲勞耐久性測試后發(fā)現(xiàn),新型IOL各個(gè)方面均符合國家標(biāo)準(zhǔn)(YY-0290)。CCK-8實(shí)驗(yàn)證明,改性后人工晶狀體對人晶狀體上皮細(xì)胞和人視網(wǎng)膜色素上皮無明顯毒性作用。體外殺菌實(shí)驗(yàn)證明,載藥型IOL可有效殺死表皮葡萄球菌。結(jié)論：通過靜電層層自組裝法成功制備出表面(透明質(zhì)酸／妥布霉素(或阿米卡星)-聚賴氨酸)。多層膜修飾的新型人工晶狀體,該多層膜的質(zhì)量、厚度可隨層數(shù)增加實(shí)現(xiàn)指數(shù)增長模式。所使用的該種改性方法不僅提高了IOL表面親水性,且不影響表面形貌及粗糙度,改性后IOL光學(xué)、力學(xué)性能符合國家標(biāo)準(zhǔn)(YY-0290),對于體外人晶狀體上皮細(xì)胞和人視網(wǎng)膜色素上皮細(xì)胞無明顯毒性作用,在體外實(shí)驗(yàn)中證明具備殺滅表皮葡萄球菌的效果。這種新型載藥型人工晶狀體有望用于防治白內(nèi)障術(shù)后眼內(nèi)炎的發(fā)生。
[Abstract]:Objective: to study the physical and chemical properties, optical and mechanical properties, cytotoxicity and bactericidal properties of the modified intraocular lens (IOL) by electrostatic layer self-assembly method. Methods: tobramycin and amikacin were used as loading drugs by using subatmospheric plasma technique and electrostatic layer self-assembly technique. The polyimide- (hyaluronic acid-polylysine / tobramycin or amikacin) was assembled on the intraocular lens surface. Its hydrophilicity was measured by contact angle measurement. Quartz crystal microbalance (QCM) was used to simulate the whole assembly process. The mass, thickness and viscoelastic energy of the self-assembled films were measured with the increase of the number of layers, and the exponential mode growth was verified. The surface morphology of the modified intraocular lens was measured by field emission scanning electron microscope (SEM) and atomic force microscope (AFM), and the surface roughness was calculated. The surface element composition of the modified IOL was analyzed by X- ray photoelectron spectroscopy (XPS) to verify the success of the assembly process. The modified IOL was tested by SFDA (YY-0290) national standard for IOL quality, including image quality, light focus, spectral transmittance and dynamic fatigue durability. The culture medium of modified intraocular lens was co-cultured with human lens epithelial cells and human retinal pigment epithelial cells. The toxicity of these two cells was detected by CCK-8 experiment. The modified intraocular lens was co-cultured with Staphylococcus epidermidis. The quantity of live and dead bacteria was observed by fluorescent dye kit and the bactericidal effect of IOL was detected in vitro. Results: the hydrophilicity of modified IOL was greatly improved by measuring contact angle. By simulating the assembly process by QCM, the success of the assembly was proved, and the quality and thickness of the surface matter of IOL increased exponentially with the increase of the number of layers by improving the conditions of the assembly system, which greatly improved the modification efficiency and drug loading. Field emission scanning electron microscopy (SEM) and atomic force microscope (AFM) showed that the surface morphology and roughness of the modified IOL showed no obvious change. XPS showed that the change of surface element composition was the result of successful assembly. It was found that all aspects of the modified IOL were in accordance with the national standard (YY-0290). CCK-8 experiment proved that the light coke, image quality, spectral transmittance and dynamic fatigue durability of the modified IOL were all in line with the national standard (YY-0290). The modified intraocular lens has no toxic effect on human lens epithelial cells and retinal pigment epithelium. In vitro bactericidal test showed that drug-loaded IOL could effectively kill Staphylococcus epidermidis. Conclusion: the surface (hyaluronic acid / tobramycin (or amikacin)-polylysine) was successfully prepared by electrostatic layer self-assembly. The mass and thickness of the multilayer IOL can increase exponentially with the increase of the number of layers. The modified method not only improves the surface hydrophilicity of IOL, but also does not affect the surface morphology and roughness. The mechanical properties were in accordance with the national standard (YY-0290) and had no obvious toxicity to human lens epithelial cells and human retinal pigment epithelial cells in vitro. It was proved in vitro that it had the effect of killing Staphylococcus epidermidis. This new drug-loaded intraocular lens is expected to be used to prevent and treat endophthalmitis after cataract surgery.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R779.6;R318.1

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