MCM-41/PAA的制备及释药性能

采用微波辅助法合成介孔分子筛(mesoporous molecular sieve)MCM-41,将其与丙烯酸(acrylic acid,AA)经原位聚合,制备具有pH敏感性的新型复合材料MCM-41/聚丙烯酸(polyacrylic acid,PAA)。通过X射线衍射、Fourier红外分析、热重分析、N2吸附/脱附等表征材料的结构和性能,证明合成了一种新型高分子复合材料。以抗压利尿药物氢氯噻嗪为模型药物,通过液体紫外法研究复合材料的载药性能及其在人工胃液(pH=1.2)和人工肠液(pH=6.8)条件下的释药性能。结果显示:MCM-41/PAA的载药量达51.75%,在人工胃液和人工肠液的体外模拟释药过程中显示出良好的pH控释的敏感性。这种材料可以用于肠道靶向控释领域。     

NH2-MCM-41的改性及其pH响应性释药的研究

采用正硅酸乙酯（TEOS）和3-氨丙基三乙氧基硅烷（APTES）通过共缩聚法合成介孔二氧化硅（MCM-41）。首先对其氨基修饰,再通过有机合成接枝—R基团（—R：—CHO、—OH、—CH₃、—COOH）,制备得到Me-Ph-NH-MCM-41、OHC-Ph-NH-MCM-41、HO-Ph-NH-MCM-41、HOOC-Ph-NH-MCM-41四种不同的药物载体。利用FT-IR、Zeta电位、XRD和SEM对其结构和形貌表征,结果表明NH₂-MCM-41改性成功。以罗丹明B（RhB）为模型进行载药性能测试,并考察了此释药系统在模拟不同pH的体液下的敏感释药行为,同时探究了不同—R基团对释药的影响。结果显示,四种载体在中性条件下几乎不发生药物释放,通过改变环境体系pH可以有效控制药物释放,其释药行为可以用Korsmeyer-Peppas动力学模型来描述。实验表明,释药量：RhB@HOOC-Ph-NH-MCM-41>RhB@OHC-Ph-NH-MCM-41>RhB@HO-Ph-NH-MCM-41>RhB@Me-Ph-NH-MCM-41,不同—R基团的药物载体的pH响应性不同,其中RhB@HOOC-Ph-NH-MCM-41释药量在pH=1.2时可达57.87%,在用于药物智能控释材料方面具有一定的应用潜力。     

硅基纳米材料结合阿司匹林的缓释作用研究

本文在碱性条件下,硅酸钠作为硅源,十六烷基三甲基溴化铵(CTAB)作为结构模板剂,利用水合晶化法合成了纯硅源的MCM-41介孔分子筛.采用浸渍法将阿司匹林组装在MCM-41六方形孔道中,制备出新型载药Aspirin/MCM-41复合物。采用X射线粉末衍射(XRD)和傅里叶红外光谱(FT-IR)表征手段对合成的新型功能化介孔材料进行表征。MCM-41分子筛与阿司匹林的相互作用为研发以MCM-41分子筛为载体的载药体系提供了理论依据。     

温度-pH双重敏感性嵌段共聚物胶束的制备及释药性能研究

RAFT法合成兼具温度-pH双重敏感性嵌段共聚物。以嵌段共聚物为载体,吲哚美辛为模型药物,透析法制备载药胶束并模拟在人体环境中的药物释放,考察载体的释药性能;FT-IR表征嵌段共聚物及载药胶束;UV法测定聚合物LCST及相变pH,并进行载药胶束的体外释药研究。一系列测试表明载药胶束在人体生理温度(37℃)下,酸性环境的药物释放速率和累积释放量要比碱性环境下小很多。嵌段共聚物兼具温度-pH双重敏感性,可作为药物载体,在药物缓释控释方面有潜在的应用。     

甲硝唑/MCM-41载药体系的制备及缓释性能的研究

试验制备甲硝唑/MCM-41载药体系,并研究了甲硝唑在模拟胃液中的释放情况。采用阳离子表面活性剂十六烷基三甲基溴化铵(CTAB)为模板剂,以正硅酸乙酯为硅源制备MCM-41,并通过浸渍法将甲硝唑组装在MCM-41孔道内,利用XRD、紫外对MCM-41和甲硝唑/MCM-41载药体系进行表征。通过紫外法测定组装体在人工胃液中的释放行为,甲硝唑在人工胃液中12小时释放达72.8%,表明MCM-41分子筛对甲硝唑有较好的缓释作用。     

苝四羧酸酐和聚丙烯酸包裹SiO2微球的制备与表征及其在布洛芬控释中的应用

用致密的纳米二氧化硅球(DNSS)作为载体,通过硅烷试剂(APTES)对其表面进行改性,并引入荧光分子3,4,9,10-苝四羧酸酐(PTD)和聚丙烯酸(PAA)分别得到APTES-DNSS、PTD@DNSS和PAA@DNSS 3种有机-无机杂化材料。采用XRD、FT-IR、SEM、TG、PL等分析手段分别对上述材料的结构特征和织构参数以及热稳定性和荧光性能进行了表征。并以布洛芬(IBU)为模型药物,重点考察了以PAA@DNSS为载体的pH敏感释药性能和发光行为。结果表明通过APTES改性以及表面嫁接PTD和PAA并不能改变DNSS的球形特征和约250 nm的颗粒尺寸,但是通过嫁接PTD赋予了样品PTD@DNSS的荧光性能,分别在400 nm和450 nm附近出现两个发射峰,进一步负载PAA后,样品PAA@DNSS则具有较强的pH敏感释药性能,特别是在pH 7. 4的释药条件下,样品PAA@DNSS不仅具有较高的释药率,而且保持较强的荧光性能。上述结果说明嫁接在APTES-DNSS表面的PAA和PTD对药物释放性能和发光行为存在着较强的表面效应。     

茴拉西坦/MCM-48载体的制备及释药性能研究

为了提高难溶性药物的口服生物利用度,采用水热合成法制备了MCM-48介孔二氧化硅载体材料,利用浸渍法将水难溶性药物茴拉西坦负载于MCM-48载体上。利用扫描电子显微镜(SEM)、透射电子显微镜(TEM)、激光粒度仪、小角X射线衍射(XRD)、N_2吸附-脱附、红外光谱(IR)、差热-热重(DTA-TG)对载药前后MCM-48的表面形貌、粒径、孔径、孔容、比表面积、晶胞参数等进行测试,结果表明,MCM-48外形为球形颗粒,介孔结构为三维立方结构,孔径3.55 nm,孔容及比表面积分别为0.86 cm³/g和764 m3/g和764 m²/g;MCM-48负载茴拉西坦的载药量为16%,载药后药物以非晶态装载于介孔孔道中或吸附于载体表面,没有影响MCM-48的骨架结构,但使孔径、孔容及比表面积下降。通过在不同pH溶液中载药MCM-48与茴拉西坦原料药的溶出度比较发现,MCM-48载体能够提高茴拉西坦的溶出速率。     

茴拉西坦/MCM-48载体的制备及释药性能研究

为了提高难溶性药物的口服生物利用度,采用水热合成法制备了MCM-48介孔二氧化硅载体材料,利用浸渍法将水难溶性药物茴拉西坦负载于MCM-48载体上。利用扫描电子显微镜(SEM)、透射电子显微镜(TEM)、激光粒度仪、小角X射线衍射(XRD)、N_2吸附-脱附、红外光谱(IR)、差热-热重(DTA-TG)对载药前后MCM-48的表面形貌、粒径、孔径、孔容、比表面积、晶胞参数等进行测试,结果表明,MCM-48外形为球形颗粒,介孔结构为三维立方结构,孔径3.55 nm,孔容及比表面积分别为0.86 cm~3/g和764 m~2/g;MCM-48负载茴拉西坦的载药量为16%,载药后药物以非晶态装载于介孔孔道中或吸附于载体表面,没有影响MCM-48的骨架结构,但使孔径、孔容及比表面积下降。通过在不同pH溶液中载药MCM-48与茴拉西坦原料药的溶出度比较发现,MCM-48载体能够提高茴拉西坦的溶出速率。     

硬脂酸/MCM-41复合相变材料研究

以硬脂酸为相变材料,介孔分子筛MCM-41为载体,采用溶液浸渍法制备了硬脂酸/MCM-41复合相变储能材料。应用SEM和TEM测试了复合材料的微观结构,利用TG-DSC分析了复合材料的相变温度、相变潜热及相变可逆性,通过FT-IR对复合材料的兼容性进行了表征。结果表明,复合材料表面具有多孔结构,改善了复合材料的相变可逆性,复合相变储能材料中硬脂酸的最大质量分数为50%,相变温度为57.8℃,相变潜热为276.4 J/g。分析表明,硬脂酸与MCM-41间是简单的嵌合关系,复合材料具有良好的热稳定性和兼容性。     

石蜡/MCM-41复合相变材料的结构及热性能

以石蜡为相变材料、SiO2介孔分子筛MCM-41为载体,采用溶液浸渍法制备了石蜡/MCM-41复合相变储能材料。应用SEM与TEM测试了复合材料的微观结构,利用TG-DSC测定了复合材料的相变温度、相变潜热及相变可逆性,通过FTIR对复合材料的兼容性进行了表征。实验表明,复合材料表面孔结构改善了相变可逆性,复合相变储能材料中石蜡的适宜质量分数为40%,相变温度为66.6℃,相变潜热为135.3 J/g。石蜡与MCM-41间是简单的嵌合关系,复合材料具有良好的热稳定性和兼容性。     

改性MCM-41分子筛的合成与亚甲基蓝吸附性能

选用TEOS（正硅酸乙酯）做为硅源,CTAB（十六烷基三甲基溴化铵）做为表面活性剂,在碱性条件下水热合成MCM-41。实验采用3-氨丙基三甲基硅烷对MCM-41进行改性,成功得到氨基改性介孔材料NH₂-MCM-41吸附剂,并使用X射线衍射（XRD）对其做了表征。考察了各种实验条件下,比如温度、吸附剂的量、pH、亚甲基蓝初始浓度等条件下MCM-41和NH₂-MCM-41对水溶液中亚甲基蓝（MB）的吸附能力。MCM-41和氨基改性介孔材料NH₂-MCM-41均为平面六方介孔结构。结果表明,温度和pH是影响MCM-41和NH₂-MCM-41对亚甲基蓝吸附的最主要的因素。随着温度的升高,材料吸附能力增强,而过高或者过低的pH都会降低MCM-41和NH₂-MCM-41对亚甲基蓝的吸附能力。     

MCM-41介孔材料的合成条件和特性对吸附镉离子的影响

以气相氧化硅为硅源,十六烷基三甲基溴化铵(cetyl trimethyl ammonium bromide,CTAB)为模板剂,分别在碱性[氢氧化钠(NaOH),四乙基氢氧化铵,tetraethyl ammonium hydroxide,(C2Hs)4NOH(TEAOH)]和酸性介质条件[盐酸(HCl)]T水热合成了MCM-41有序介孔材料MCM-41-N,MCM-41-T和MCM-41-H.用X射线衍射、氮气吸附-脱附等手段对比分析了合成的3种MCM-41介孔材料的物相、比表面积、孔径、孔体积等,发现酸性介质中合成的介孔材料的孔径最大.在此基础上,利用MCM-41介孔材料对比研究了处理含镉离子(Cd2 )废水的效果和机理,确定了不同介孔材料用量、不同初始pH值条件下MCM-41介孔材料对水中Cd2 的吸附率和吸附量.结果表明:介孔材料用量相同时,溶液pH值的增大有利于提高3种MCM-41介孔材料对水中Cd2 的处理效果.在pH值从7.0到8.0的过程中,其吸附率有1个突变,MCM-41-T的Cd2 吸附率从35.65%提高到62.15%;MCM-41-N的从38.80%提高到69.40%;MCM-41-H的从50.22%提高到73.47%.孔径最大的MCM-41-H对Cd2 的吸附效果最佳,最大吸附率为89.56%,最大吸附容量为8.57 mg/g.吸附溶液pH值的大小和介孔材料的孔径尺寸是决定吸附量大小的关键因素,因此,重点应通过优化合成工艺提高介孔材料的孔径.     

Effect of particle morphology and pore size on the release kinetics of ephedrine from mesoporous MCM-41 materials

Ephedrine was loaded onto siliceous mesoporous materials of different pore sizes, and the corresponding drug release into simulated body fluid at pH 7.4 and 37?°C was measured against time over a period of 72?h. The mesoporous materials designated MCM-41(C_N) were prepared at different pore sizes using a self-assembly mechanism. The pore size was controlled by the use of alkyltrimethylammonium bromide (C_NTAB) surfactants having different alkyl chain lengths (C₁₀, C₁₂, and C₁₄). The three mesoporous materials showed good ephedrine-loading capacities from dry ethanolic solutions, which slightly increased with the pore size of MCM-41(C_N). From the drug release profiles, the overall release of ephedrine followed the order: MCM-41(C₁₂)?>?MCM-41(C₁₄)?>?MCM-41(C₁₀), with the release of ephedrine attaining 92% of the drug load from MCM-41(C₁₂). Ephedrine release approached 60% of the drug load in 6?h and 92% in 20?h. The results of in vitro release kinetics indicate that pore size is not the only factor affecting ephedrine release, but also pore channel length and overall particle morphology.     

Study on modification of NH2-MCM-41 and its pH-responsive drug release

Mesoporous silica (MCM-41) was synthesized by copolycondensation of tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES). Firstly, it was modified with amino group. Then, four different drug carriers, Me-Ph-NH-MCM-41, OHC-Ph-NH-MCM-41, HO-Ph-NH-MCM-41, and HOOC-Ph-NH-MCM-41, were synthesized by grafting —R group (—R: —CHO, —OH, —CH₃, —COOH), respectively. FT-IR, SEM, Zeta potential, and XRD were used to characterize its structure and morphology, indicating the successful synthesis of modified MCM-41. Rhodamine B (RhB) was used as a model for drug loading performance testing and the sensitive drug release behavior of this drug release system under different pH simulated humors was investigated. The effects of different —R groups on drug release were also explored. The results show that the four carriers hardly release drugs under neutral conditions. The drug release can be effectively controlled by changing the pH of the environmental system. The drug release behavior can be described by the Korsmeyer-Peppas kinetic model. The experiment showed that the drug release amount: RhB@HOOC-Ph-NH-MCM-41>RhB@OHC-Ph-NH-MCM-41>RhB@HO-Ph-NH-MCM-41>RhB@Me-Ph-NH-MCM-41. The pH-response of drug carriers with different —R groups was different, and the drug release amount of RhB@HOOC-Ph-NH-MCM-41 reached 57.87% at pH = 1.2, which has some potential applications in intelligent controlled release materials of drugs.     

3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol

The present work was proposed not only to exploit the potential of 3D cage-like mesoporous silica SBA-16 with a well-defined spherical morphology as a carrier for poorly soluble drugs, but also to compare the drug loading and release properties of 3D cubic SBA-16 with that of classic 2D hexagonal MCM-41. SBA-16 microsphere with highly ordered mesostructures was synthesized by a facile method using block co-polymer F127 as template, cetyltrimethylammonium bromide (CTAB) as co-template and tetraethyl orthosilicate (TEOS) as silica source. Carvedilol (CAR), an antihypertensive agent, was used as a model drug and loaded into mesoporous silica via solvent deposition method at drug-silica ratio of 1:3. In vitro dissolution was performed in both simulated intestinal fluid (SIF, pH 6.8) and simulated gastric fluid (SGF, pH 1.2). Of particular interest was that in SIF both MCM-41 and SBA-16 samples exhibited promoted dissolution profile for CAR as compared to its corresponding crystalline form which exhibited poor dissolution behavior. This dissolution-enhancing effect might be due to the non-crystalline state and increased surface area of confined CAR as well as the hydrophilic nature of silica. In comparison with MCM-41, SBA-16 displayed a more rapid release profile in both SIF and SGF, which may be ascribed to the 3D interconnected pore networks and the highly accessible surface areas. The suitability of the utilization of SBA-16 microsphere as carriers will open new avenues for the formulation of poorly soluble drugs.     

京尼平交联大豆蛋白/壳聚糖复合凝胶的控释

利用天然无毒的京尼平交联大豆蛋白(SB)和壳聚糖(CS)制备复合水凝胶(HD)并用作茶碱的控释载体。同时对其在模拟胃肠液和pH7.4缓冲液（PBS）中的控释特性进行了研究。结合扫描电镜和红外光谱以及核磁共振表征了复合凝胶的表观形态和结构。结果表明,复合水凝胶中大豆蛋白和壳聚糖通过京尼平发生了明显的交联作用,并呈现致密的片层结构。复合凝胶在模拟胃肠液和pH7.4PBS中均呈现溶胀现象,在模拟胃液中的溶胀度较低。而且凝胶在pH1.2模拟胃液中的释放量比模拟肠液和pH7.4PBS液中的低,并发现该凝胶具有pH响应,在120 h内可实现对茶碱的可控释放。因此,这种京尼平交联的复合凝胶具有作为药物在胃肠道中定向运送载体的潜力。     

The synergistic cooperation between MCM-41 and azithromycin: a pH responsive system for drug adsorption and release

The capability of MCM-41 silica for accepting and delivering poorly soluble azithromycin (AZT) in water is reported as robust drug delivery system. This property has been evidenced by using two MCM-41 samples with different pore sizes as hosts of AZT. The choice of this macrolide antibiotic is due not only to its low bioavailability but also to its molecular size which lies in the range of pore diameter of MCM-41s. The drug was loaded inside the pore voids of the mesoporous when MCM-41 was stirred at AZT solution, based on XRD, Nitrogen adsorption–desorption isotherms, TGA analysis data and FT-IR spectroscopy. The amount of AZT stored inside the pores of MCM-41 s was between 22 and 25 wt%. The loaded drug was released in different rates from the particles by changing the pH (1.7 and 7.4) to give a smart pH-responsive carrier system. The drug release kinetics was fitted to Korsmeyer–Peppas and Higuchi models which indicated that the rate of drug release was controlled by the diffusion of the drug. The result of the present study confirms that the controlled adsorption and liberation of AZT may improve the oral bioavailability of poor water soluble AZT. This study demonstrates the feasibility of designing reliable drug delivery systems by appropriate choice of the matrix and the organic molecule. In general, MCM-41 is a promising matrix for AZT adsorption with different application from drug delivery to wastewater filtration.