【作者】 梁枫；

【导师】 杨文胜；

【作者基本信息】 吉林大学 ， 物理化学， 2021， 博士

【摘要】 姜黄素(Cur)因其具有多种的生物活性及独特的光学性质,在食品药品、荧光成像、离子检测、光动力治疗等领域有广泛的应用前景。姜黄素在有机溶剂中溶解性较好,而在水中溶解度很低,导致其生物利用率较低。在强碱性条件下姜黄素可以发生去质子化,从而提高其在水中溶解度,但去质子化后姜黄素稳定性变差,难以满足实际应用的需求。将姜黄素复合到水溶性胶体粒子中,一方面可以提高其在水中的分散能力,另一方面可以有效提高其稳定性。二氧化硅粒子由于其良好的生物相容性以及化学和胶体稳定性,是一类理想的姜黄素复合载体。在醇/水混合溶剂中利用氨水催化正硅酸四乙酯(TEOS)水解缩合,也就是我们熟知的Stober法,是目前制备二氧化硅粒子最为常用的方法之一。在这个反应体系中,由于二氧化硅粒子及姜黄素均带有负电,静电排斥作用的存在导致姜黄素难以被复合到二氧化硅粒子中。为了解决这一问题,我们引入可以与姜黄素和二氧化硅同时发生相互作用的表面活性剂十六烷基三甲基溴化铵(CTAB),系统研究了醇/水混合体系中氨水及CTAB对姜黄素去质子化和溶解分散过程以及二氧化硅粒子生长过程的影响,以期实现二氧化硅粒子对姜黄素的高效复合和有效保护,为姜黄素的开发利用提供实验依据。首先我们对醇/水混合体系中氨水及CTAB浓度对姜黄素去质子化及溶解分散过程进行了系统研究,发现随着氨水浓度的提高,姜黄素逐渐发生去质子化,其溶解分散能力得到改善,但稳定性明显下降。CTAB的加入可以在一定程度上促进姜黄素的去质子化过程,并对其质子化过程具有一定的抑制作用。当溶液中CTAB浓度高于其临界成胶束浓度(CMC)时,姜黄素可以被分散到胶束的疏水区域,同时提高其分散能力和稳定性。向含有合适氨水及CTAB浓度的姜黄素醇/水混合溶液中加入TEOS,可以实现二氧化硅粒子的原位生长,从而以CTAB为媒介将姜黄素复合到二氧化硅粒子中。研究发现随着溶液中CTAB浓度的升高,所生成的粒子其形貌逐渐由球形演变成椭球形,姜黄素的复合效率呈现先上升后下降的趋势。在优化的反应条件下,二氧化硅粒子对姜黄素的复合效率可以高达93%。在复合到二氧化硅粒子中以后,姜黄素的稳定性及发光效率均得到了明显改善。与CTAB胶束负载的姜黄素相比,复合到二氧化硅粒子中姜黄素对溶液中铜离子具有更好的响应能力。将CTAB胶束预先复合到二氧化硅粒子中,然后将其加入到姜黄素溶液中,可以实现对姜黄素复合过程的进一步调控。通过改变醇水比,我们可以得到CTAB胶束以类晶态及无定形态两种不同形式存在的二氧化硅粒子。研究发现,两种含有不同微环境的二氧化硅粒子均可以实现对姜黄素的高效、快速复合,并改善其稳定性。与处于无定形微环境中的姜黄素相比,处于类晶态微环境中的姜黄素对铜离子具有更好的响应能力。研究结果,为姜黄素/二氧化硅复合粒子制备以及姜黄素稳定性和光学性能调控提供了新的实验方法,为姜黄素的开发利用提供了有益的实验依据。上述具有不同微环境的两种二氧化硅粒子也可以实现对不同染料的高效负载。同时负载有姜黄素和荧光素的粒子,可以基于荧光素与姜黄素之间的激发态共振能量转移,形成多色二氧化硅粒子。这种多色粒子既可以通过荧光强度也可以通过发光颜色对环境pH和铜离子浓度进行监测。研究结果,为多色姜黄素/二氧化硅粒子的制备提供了有效的实验方法,并为其在高通量、可视化检测中的应用提供实验依据。更多还原

【Abstract】 Curcumin(cur)has widespread applications in food and drug,fluorescence imaging,ion detection,photodynamic therapy and other fields because of its various biological activities and unique optical properties.Curcumin has low bioavailability due to its good solubility in organic solvents,but low solubility in water.Curcumin can be deprotonated under strong alkaline conditions,which can improve its solubility in water,but the stability of deprotonated curcumin is poor,which is insufficient to meet the needs of practical application.Incorporating curcumin into colloidal particles with good dispersion in water can improve its dispersibility in water and effectively improve its stability.Silica particles are an ideal type of carrier for curcumin due to their good biocompatibility and chemical/colloidal stability.Using ammonia to catalyze the hydrolysis and condensation of tetraethylorthosilicate(TEOS)in an ethanol/water mixture,known as the Stober method,is currently one of the most commonly used methods for preparing silica particles.In this reaction system,curcumin is difficult to be incorporated into silica particles due to electrostatic repulsion between the negatively charged silica particles and curcumin.To solve this problem,we introduced the surfactant hexadecyltrimethylammonium bromide(CTAB),which can interact with curcumin and silica simultaneously.We systematically studied the effect of ammonia and CTAB on the deprotonated and dissolution or dispersion process of curcumin,and the growth of silica particles in the ethanol/water mixture.It is expected to realize the high loading efficient and effective protection of curcumin by silica particles,which can provide the experimental basis for the development and utilization of curcumin.Firstly,we conducted a systematic study on the deprotonation and dissolution/dispersion process of curcumin with different concentrations of ammonia and CTAB in ethanol/water mixture.It was found that with the increase of ammonia concentration,curcumin gradually undergoes deprotonation,and its dissolution/dispersion ability is adequate,but its stability decreased significantly.The addition of CTAB can promote the deprotonation process of curcumin to a certain extent,and inhibit its protonation process to a certain extent.When the concentration of CTAB in the solution is higher than its critical micelle concentration(CMC),curcumin can be dispersed into the hydrophobic area of micelles,which can improve its dispersibility and stability.Adding TEOS to a curcumin ethanol/water mixture containing appropriate concentrations of ammonia and CTAB can realize in-situ growth of silica particles,thus curcumin can be incorporated into silica particles with the assist of CTAB.It was found that with the increase of CTAB concentration in the solution,the morphology of the particles gradually evolved from spherical to ellipsoidal,and the loading efficiency of curcumin increased first and then decreased.Under the optimized reaction conditions,the loading efficiency of curcumin in silica particles can be as high as 93%.After being incorporated into silica particles,the stability and luminous efficiency of curcumin have been significantly improved.Compared with CTAB micelle-loaded curcumin,curcumin loaded in the silica particles is more sensitive to copper ions.CTAB micelles were firstly into silica particles,and then the particles were added into curcumin solution to further regulate the incorporation of curcumin.By changing the concentration of CTAB,we can obtain silica particles in which CTAB micelles exist in two different forms: quasi-crystalline phase and amorphous phase.It is found that both two kinds of silica particles with different microenvironments can achieve efficient and rapid incorporation of curcumin and improve its stability.Compared with curcumin in the amorphous microenvironment,curcumin in the quasi crystalline microenvironment is more sensitive to copper ions.The above-mentioned two kinds of silica particles with different microenvironments can also achieve high loading efficiency of different dyes.The silica particles incorporated with curcumin and fluorescein can exhibit multicolor emission based on the excited state resonance energy transfer between curcumin and fluorescein.This kind of multicolor particle can monitor environmental pH and copper ion concentration through fluorescence intensity and emission color,which provides a foundation for the application of curcumin in high-throughput visual detection.更多还原