Pickering乳液在药物释放与酶促反应中的应用研究
发布时间：2018-10-15 11:24
【摘要】：皮克林(Pickering)乳液是由固体颗粒替代传统表面活性剂稳定的一类乳液。由于其具有高稳定性、颗粒浸润性可控、绿色和环境友好等优势,因此在药物释放和酶促反应领域应用广泛。将具有合适浸润性的TiO_2纳米颗粒自组装于乳液界面,形成一层围绕着液滴周围的致密堆积的颗粒层,能够作为一种储存稳定,药物保护和可控释放的有效载体。本论文主要开展颗粒乳化剂表面浸润性变化导致的Pickering乳液不稳机理以及其在药物释放和界面酶催化中的应用基础研究。在Pickering乳液释放方面,本论文研究了光触发的Pickering乳液按需释放方式以及光致乳液不稳机理。作者开发了一种用于稳定油包水(W/O)乳液的TiO_2纳米颗粒乳化剂,首先,利用紫外光定制具有合适浸润性的TiO_2纳米颗粒;然后,将其自组装于油水界面稳定W/O乳液并实现药物包封;之后,紫外光照引起颗粒表面浸润性转变使得颗粒从乳液界面脱落,乳液变得不稳定最终破乳分相,包封于内水相的药物被释放出来。在药物释放探究中,我们选择了一种传统中药-黄芪作为模型药物评价乳液的包封和释放行为,分别研究了颗粒浓度、光照波长和光照强度改变对乳液不稳机理的影响。研究发现,TiO_2纳米颗粒浓度从1增大到2和3 wt%,液滴直径从280微米降低到180 μm和130μm,聚并时间从12 h延长至24 h和48 h;在1 wt%TiO_2纳米颗粒浓度下,只有紫外光能导致乳液不稳最终相分离,而可见光和黑暗不能引起乳液聚并;紫外照射波长从254 nm增大到365 nm,破乳时间从12 h增大到36 h;紫外照射强度从200 μw·cm~(-2)减小到100 μw·cm~(-2)和50 μw·cm~(-2),乳液相分离时间从12 h延长至32h和72h。考虑到在生命科学中紫外光的应用限制,作者通过制备掺氮TiO_2纳米颗粒建立了具有可见光响应特性的乳液。同时,TiO_2纳米颗粒也是最常用的无机防晒剂之一,作者将光致乳液不稳机理用于开发和研制具有高倍防晒、易清洗和可控释放的防晒霜乳液配方。该研究成果在制药工程和精细化工等领域具有潜在的应用前景。在Pickering乳液跨界面酶促反应部分,基于浸润性调控乳液稳定性部分的研究基础,作者通过不同碳链长度硅烷的表面改性,制备了一系列不同浸润性的介孔SiO_2颗粒来固定化脂肪酶,并将其自组装于油水界面稳定Pickering乳液,强化了跨乳液界面的酶促反应。仅需颗粒乳化剂表面浸润性的改变,即可调控乳液反应体系的界面面积,进而强化了跨界面的酶促反应。研究发现,碳链长度分别为C0(不改性的),C3(3个碳),C6(6个碳),C8(8个碳),C10(10个碳)和C12(12个碳)时,其三相接触角分别为25°,109°,118°,95°,130°和145°;酶促反应转化率C8C3C6C10C12C0;可以看到,C8颗粒改性的介孔SiO_2颗粒三相接触角最接近90°,稳定的乳液液滴直径最小,乳液层厚度最大,总的反应面积最大,对Pickering乳液酶促反应强化效果最好。更重要的是,该Pickering乳液通过低速离心即可实现底物、产物和酶的分离回收,并且介孔SiO_2颗粒能保护酶免受有机试剂的侵蚀,重复使用6次后,仍保持较高的催化活性。本研究的介孔硅固载酶稳定的Pickering乳液系统对于两相酶促反应是一个创新且可调控的反应体系,为两相界面酶促反应提供了借鉴和思路。
[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 掳, 109 掳, 118 掳, 95 掳, 130 掳 and 145 掳, respectively; enzymatic reaction conversion was C8C3C6H40.5C0; it could be seen that the carbon chain length was 25 掳, 109 掳, 118 掳, 95 掳, 130 掳 and 145 掳, respectively. The three-phase contact angle of the mesoporous SiO _ 2 particles modified by the C8 particles is closest to 90 掳, 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.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.1
本文编号：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 掳, 109 掳, 118 掳, 95 掳, 130 掳 and 145 掳, respectively; enzymatic reaction conversion was C8C3C6H40.5C0; it could be seen that the carbon chain length was 25 掳, 109 掳, 118 掳, 95 掳, 130 掳 and 145 掳, respectively. The three-phase contact angle of the mesoporous SiO _ 2 particles modified by the C8 particles is closest to 90 掳, 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.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.1
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