Pickering乳液在藥物釋放與酶促反應(yīng)中的應(yīng)用研究
發(fā)布時間：2018-10-15 11:24
【摘要】：皮克林(Pickering)乳液是由固體顆粒替代傳統(tǒng)表面活性劑穩(wěn)定的一類乳液。由于其具有高穩(wěn)定性、顆粒浸潤性可控、綠色和環(huán)境友好等優(yōu)勢,因此在藥物釋放和酶促反應(yīng)領(lǐng)域應(yīng)用廣泛。將具有合適浸潤性的TiO_2納米顆粒自組裝于乳液界面,形成一層圍繞著液滴周圍的致密堆積的顆粒層,能夠作為一種儲存穩(wěn)定,藥物保護(hù)和可控釋放的有效載體。本論文主要開展顆粒乳化劑表面浸潤性變化導(dǎo)致的Pickering乳液不穩(wěn)機(jī)理以及其在藥物釋放和界面酶催化中的應(yīng)用基礎(chǔ)研究。在Pickering乳液釋放方面,本論文研究了光觸發(fā)的Pickering乳液按需釋放方式以及光致乳液不穩(wěn)機(jī)理。作者開發(fā)了一種用于穩(wěn)定油包水(W/O)乳液的TiO_2納米顆粒乳化劑,首先,利用紫外光定制具有合適浸潤性的TiO_2納米顆粒;然后,將其自組裝于油水界面穩(wěn)定W/O乳液并實現(xiàn)藥物包封;之后,紫外光照引起顆粒表面浸潤性轉(zhuǎn)變使得顆粒從乳液界面脫落,乳液變得不穩(wěn)定最終破乳分相,包封于內(nèi)水相的藥物被釋放出來。在藥物釋放探究中,我們選擇了一種傳統(tǒng)中藥-黃芪作為模型藥物評價乳液的包封和釋放行為,分別研究了顆粒濃度、光照波長和光照強(qiáng)度改變對乳液不穩(wěn)機(jī)理的影響。研究發(fā)現(xiàn),TiO_2納米顆粒濃度從1增大到2和3 wt%,液滴直徑從280微米降低到180 μm和130μm,聚并時間從12 h延長至24 h和48 h;在1 wt%TiO_2納米顆粒濃度下,只有紫外光能導(dǎo)致乳液不穩(wěn)最終相分離,而可見光和黑暗不能引起乳液聚并;紫外照射波長從254 nm增大到365 nm,破乳時間從12 h增大到36 h;紫外照射強(qiáng)度從200 μw·cm~(-2)減小到100 μw·cm~(-2)和50 μw·cm~(-2),乳液相分離時間從12 h延長至32h和72h�？紤]到在生命科學(xué)中紫外光的應(yīng)用限制,作者通過制備摻氮TiO_2納米顆粒建立了具有可見光響應(yīng)特性的乳液。同時,TiO_2納米顆粒也是最常用的無機(jī)防曬劑之一,作者將光致乳液不穩(wěn)機(jī)理用于開發(fā)和研制具有高倍防曬、易清洗和可控釋放的防曬霜乳液配方。該研究成果在制藥工程和精細(xì)化工等領(lǐng)域具有潛在的應(yīng)用前景。在Pickering乳液跨界面酶促反應(yīng)部分,基于浸潤性調(diào)控乳液穩(wěn)定性部分的研究基礎(chǔ),作者通過不同碳鏈長度硅烷的表面改性,制備了一系列不同浸潤性的介孔SiO_2顆粒來固定化脂肪酶,并將其自組裝于油水界面穩(wěn)定Pickering乳液,強(qiáng)化了跨乳液界面的酶促反應(yīng)。僅需顆粒乳化劑表面浸潤性的改變,即可調(diào)控乳液反應(yīng)體系的界面面積,進(jìn)而強(qiáng)化了跨界面的酶促反應(yīng)。研究發(fā)現(xiàn),碳鏈長度分別為C0(不改性的),C3(3個碳),C6(6個碳),C8(8個碳),C10(10個碳)和C12(12個碳)時,其三相接觸角分別為25°,109°,118°,95°,130°和145°;酶促反應(yīng)轉(zhuǎn)化率C8C3C6C10C12C0;可以看到,C8顆粒改性的介孔SiO_2顆粒三相接觸角最接近90°,穩(wěn)定的乳液液滴直徑最小,乳液層厚度最大,總的反應(yīng)面積最大,對Pickering乳液酶促反應(yīng)強(qiáng)化效果最好。更重要的是,該P(yáng)ickering乳液通過低速離心即可實現(xiàn)底物、產(chǎn)物和酶的分離回收,并且介孔SiO_2顆粒能保護(hù)酶免受有機(jī)試劑的侵蝕,重復(fù)使用6次后,仍保持較高的催化活性。本研究的介孔硅固載酶穩(wěn)定的Pickering乳液系統(tǒng)對于兩相酶促反應(yīng)是一個創(chuàng)新且可調(diào)控的反應(yīng)體系,為兩相界面酶促反應(yīng)提供了借鑒和思路。
[Abstract]:Pickering emulsions are a class of emulsions stabilized by solid particles instead of conventional surfactants. because of the advantages of high stability, controllable particle wettability, environment friendliness and the like, the invention has wide application in the field of drug release and enzymatic reaction. The TiO _ 2 nanoparticles with proper wettability are self-assembled in the emulsion interface to form a dense packed granular layer around the droplets, which can be used as an effective carrier for storage stability, drug protection and controlled release. The paper mainly studies the unstable mechanism of Pickering emulsion caused by the change of surface wettability of particle emulsifier and its application base in drug release and interfacial enzyme catalysis. In the aspect of Pickering emulsion release, the paper studied the release mode of Pickering emulsion triggered by light and the unstable mechanism of light-induced emulsion. A TiO _ 2 nano-particle emulsifier for stabilizing oil-water (W/ O) emulsion is developed. First, TiO _ 2 nano-particles with proper wettability are tailored by ultraviolet light; then, it is self-assembled in the oil-water interface to stabilize the W/ O emulsion and realize the drug encapsulation; after that, The change of the surface wettability of the particles caused by ultraviolet irradiation causes the particles to fall off the emulsion interface, and the emulsion becomes unstable and finally breaks the milk separating phase, and the medicine encapsulated in the inner water phase is released. In the study of drug release, we selected a traditional Chinese traditional medicine (TCM) as the model drug to evaluate the encapsulation and release behavior of the emulsion, and studied the effect of particle concentration, light wavelength and light intensity on the instability mechanism of the emulsion. It was found that the concentration of TiO _ 2 nanoparticles increased from 1 to 2 and 3 wt%, the droplet diameter was reduced from 280 microns to 180. m u.m and 130. m u.m, the polymerization time was extended from 12 h to 24 h and 48 h, and at 1 wt% TiO _ 2 nanoparticles, only UV light could cause the emulsion to be unstable and eventually separated, The UV irradiation wavelength was increased from 254 nm to 365 nm, and the breaking time increased from 12 h to 36 h, and the UV irradiation intensity was reduced from 200. m u.w. cm ~ (-2) to 100. m u.w 路 cm ~ (-2) and 50. m Taking into account the application limitation of ultraviolet light in life science, the authors established an emulsion with visible light response characteristics by preparing nitrogen-doped TiO _ 2 nanoparticles. At the same time, TiO _ 2 nanoparticles are also one of the most commonly used inorganic sunscreen agents, and the authors use the light-induced emulsion instability mechanism to develop and develop a sunscreen lotion formulation with high-power sun protection, moisture absorption and controlled release. The research results have potential application prospect in pharmaceutical engineering and fine chemical industry. Based on the research on the stability of the emulsion cross-interface of Pickering emulsion, the authors prepared a series of porous SiO _ 2 particles with different wettability by modifying the surface of different carbon chain length silanes to immobilize the lipase. and the enzymatic reaction of the cross-emulsion interface is enhanced by self-assembling the Pickering emulsion of the oil-water interface. The interface area of the emulsion reaction system can be adjusted by only changing the wettability of the surface of the particle emulsifier, thereby enhancing the enzymatic reaction across the interface. It was found that carbon chain lengths were C0 (unmodified), C3 (3 carbons), C6 (6 carbons), C8 (8 carbons), C10 (10 carbons), and C12 (12 carbons), respectively, and the three phases of contact were 25 擄, 109 擄, 118 擄, 95 擄, 130 擄 and 145 擄, respectively; enzymatic reaction conversion was C8C3C6H40.5C0; it could be seen that the carbon chain length was 25 擄, 109 擄, 118 擄, 95 擄, 130 擄 and 145 擄, respectively. The three-phase contact angle of the mesoporous SiO _ 2 particles modified by the C8 particles is closest to 90 擄, the diameter of the stable emulsion drops is the smallest, the thickness of the emulsion layer is the largest, the total reaction area is the largest, and the enzymatic reaction strengthening effect of the Pickering emulsion is the best. More importantly, the Pickering emulsion can realize the separation and recovery of the substrate, the product and the enzyme by low-speed centrifugation, and the mesoporous SiO2 particles can protect the enzyme from the erosion of the organic reagent, and still maintain high catalytic activity after 6 times of repeated use. The Pickering emulsion system, which is stable in porous silicon solid-carrying enzyme, is an innovative and controllable reaction system for two-phase enzymatic reaction, which provides reference and thought for the enzymatic reaction of two-phase interface.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ460.1
本文編號：2272397
[Abstract]:Pickering emulsions are a class of emulsions stabilized by solid particles instead of conventional surfactants. because of the advantages of high stability, controllable particle wettability, environment friendliness and the like, the invention has wide application in the field of drug release and enzymatic reaction. The TiO _ 2 nanoparticles with proper wettability are self-assembled in the emulsion interface to form a dense packed granular layer around the droplets, which can be used as an effective carrier for storage stability, drug protection and controlled release. The paper mainly studies the unstable mechanism of Pickering emulsion caused by the change of surface wettability of particle emulsifier and its application base in drug release and interfacial enzyme catalysis. In the aspect of Pickering emulsion release, the paper studied the release mode of Pickering emulsion triggered by light and the unstable mechanism of light-induced emulsion. A TiO _ 2 nano-particle emulsifier for stabilizing oil-water (W/ O) emulsion is developed. First, TiO _ 2 nano-particles with proper wettability are tailored by ultraviolet light; then, it is self-assembled in the oil-water interface to stabilize the W/ O emulsion and realize the drug encapsulation; after that, The change of the surface wettability of the particles caused by ultraviolet irradiation causes the particles to fall off the emulsion interface, and the emulsion becomes unstable and finally breaks the milk separating phase, and the medicine encapsulated in the inner water phase is released. In the study of drug release, we selected a traditional Chinese traditional medicine (TCM) as the model drug to evaluate the encapsulation and release behavior of the emulsion, and studied the effect of particle concentration, light wavelength and light intensity on the instability mechanism of the emulsion. It was found that the concentration of TiO _ 2 nanoparticles increased from 1 to 2 and 3 wt%, the droplet diameter was reduced from 280 microns to 180. m u.m and 130. m u.m, the polymerization time was extended from 12 h to 24 h and 48 h, and at 1 wt% TiO _ 2 nanoparticles, only UV light could cause the emulsion to be unstable and eventually separated, The UV irradiation wavelength was increased from 254 nm to 365 nm, and the breaking time increased from 12 h to 36 h, and the UV irradiation intensity was reduced from 200. m u.w. cm ~ (-2) to 100. m u.w 路 cm ~ (-2) and 50. m Taking into account the application limitation of ultraviolet light in life science, the authors established an emulsion with visible light response characteristics by preparing nitrogen-doped TiO _ 2 nanoparticles. At the same time, TiO _ 2 nanoparticles are also one of the most commonly used inorganic sunscreen agents, and the authors use the light-induced emulsion instability mechanism to develop and develop a sunscreen lotion formulation with high-power sun protection, moisture absorption and controlled release. The research results have potential application prospect in pharmaceutical engineering and fine chemical industry. Based on the research on the stability of the emulsion cross-interface of Pickering emulsion, the authors prepared a series of porous SiO _ 2 particles with different wettability by modifying the surface of different carbon chain length silanes to immobilize the lipase. and the enzymatic reaction of the cross-emulsion interface is enhanced by self-assembling the Pickering emulsion of the oil-water interface. The interface area of the emulsion reaction system can be adjusted by only changing the wettability of the surface of the particle emulsifier, thereby enhancing the enzymatic reaction across the interface. It was found that carbon chain lengths were C0 (unmodified), C3 (3 carbons), C6 (6 carbons), C8 (8 carbons), C10 (10 carbons), and C12 (12 carbons), respectively, and the three phases of contact were 25 擄, 109 擄, 118 擄, 95 擄, 130 擄 and 145 擄, respectively; enzymatic reaction conversion was C8C3C6H40.5C0; it could be seen that the carbon chain length was 25 擄, 109 擄, 118 擄, 95 擄, 130 擄 and 145 擄, respectively. The three-phase contact angle of the mesoporous SiO _ 2 particles modified by the C8 particles is closest to 90 擄, the diameter of the stable emulsion drops is the smallest, the thickness of the emulsion layer is the largest, the total reaction area is the largest, and the enzymatic reaction strengthening effect of the Pickering emulsion is the best. More importantly, the Pickering emulsion can realize the separation and recovery of the substrate, the product and the enzyme by low-speed centrifugation, and the mesoporous SiO2 particles can protect the enzyme from the erosion of the organic reagent, and still maintain high catalytic activity after 6 times of repeated use. The Pickering emulsion system, which is stable in porous silicon solid-carrying enzyme, is an innovative and controllable reaction system for two-phase enzymatic reaction, which provides reference and thought for the enzymatic reaction of two-phase interface.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ460.1
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