The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol

Objective: To explore the suitable application of MCM-41 (Mobil Composition of Matter number forty-one)-type and MCM-48-type mesoporous silica in the oral water insoluble drug delivery system.

Methods: Cilostazol (CLT) as a model drug was loaded into synthesized MCM-48 (Mobil Composition of Matter number forty-eight) and commercial MCM-41 by three common methods. The obtained MCM-41, MCM-48 and CLT-loaded samples were characterized by means of nitrogen adsorption, thermogravimetric analysis, ultraviolet-visible spectrophotometry, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and powder X-ray diffractometer.

Results: It was found that solvent evaporation method was preferred according to the drug loading efficiency and the maximum percent cumulative drug dissolution. MCM-48 with 3D cubic pore structure and MCM-41 with 2D long tubular structure are nearly spherical particles in 300–500?nm. Nevertheless, the silica carriers with similar large specific surface areas and concentrating pore size distributions (978.66?m²/g, 3.8?nm for MCM-41 and 1108.04?m²/g, 3.6?nm for MCM-48) exhibited different adsorption behaviors for CLT. The maximum percent cumulative drug release of the two CLT/silica solid dispersion (CLT-MCM-48 and CLT-MCM-41) was 63.41% and 85.78% within 60?min, respectively; while in the subsequent 12?h release experiment, almost 100% cumulative drug release were both obtained. In the pharmacokinetics aspect, the maximum plasma concentrations of CLT-MCM-48 reached 3.63?mg/L by 0.92?h. The AUC_0–∞ values of the CLT-MCM-41 and CLT-MCM-48 were 1.14-fold and 1.73-fold, respectively, compared with the commercial preparation.

Conclusion: Our findings suggest that MCM-41-type and MCM-48-type mesoporous silica have great promise as solid dispersion carriers for sustained and immediate release separately.     

Influence of pH on the sorption behaviour of uranyl ions in mesoporous MCM-41 and MCM-48 molecular sieves

The sorption of uranyl ions in mesoporous MCM-41 and MCM-48 was accomplished with the help of a direct-template-exchange route, and the progress was monitored as a function of pH of the precursor uranyl nitrate solution. Under identical conditions of synthesis, around one and a half times larger amount of uranium was found to be sorbed in MCM-48 (∼12.5 wt.%) as compared to MCM-41 (∼9.5 wt.%). Further, the powder X-ray diffraction (XRD) data revealed that the expansion of unit cell parameters and broadening of reflections of the uranium containing samples depended on the pH of the precursor uranyl solution. Likewise, the Fourier transform infrared spectroscopy (FT-IR) studies showed a progressive decrease in the frequency of the axial OUO asymmetric stretching vibrational band, ν_a(UO) of the anchored uranyl groups with the increase of pH of the exchanging uranyl solution. The presence of two bands at ∼920 and 879 cm⁻¹ for uranyl exchanged samples prepared at pH > 5 indicated the presence of trinuclear (UO₂)₃⁺₅(OH) species. The occlusion of uranium thus depends upon the pore structure of the host material and the nature and dimension of the hydrolysis species formed at a particular pH of uranyl solution. Furthermore, the template-exchange of hexavalent uranium in MCM-41 and MCM-48 not only results in the formation of bulky hydrolysis species in the mesovoids, but also substitutes (isomorphously) in the silicate matrix resulting in the formation of UMCM-41 and UMCM-48.     

Investigation of in vitro permeability and in vivo pharmacokinetic behavior of bare and functionalized MCM-41 and MCM-48 mesoporous silica nanoparticles: a burst and controlled drug release system for raloxifene

In the present work, MCM-41 and MCM-48 type of nanoparticles were successfully engineered. Effect of nanosize and amine functionalization on drug release, in vitro intestinal absorption and in vivo pharmacokinetic behavior was investigated in a comprehensive manner. The tailor-made bare and surface decorated MCM-41 and MCM-48 were synthesized and evaluated for their mesoporous skeleton, pore size, particle size, surface area, zeta potential, etc. by nitrogen sorption, DLS, TEM, etc. Incorporation of raloxifene (RLF) was affirmed using optimized immersion-solvent evaporation technique and its success confirmed by DSC, IR, and XRD analysis. TGA analysis revealed higher %grafting of amine groups on the exterior and larger RLF encapsulation into mesoporous derivate. The detailed in vitro release study revealed SGF to be the most compatible media for RLF showing an initial burst release from pristine nanoparticles and a delayed release from surface coated nanoparticles. Furthermore, release kinetics model data demonstrated Weibull and Higuchi as the best fit models for bare and amine-functionalized nanoparticles respectively. Moreover, an in vitro permeability study on Caco-2 cell line revealed higher absorption by engineered nanoparticle as compared to pure RLF and its marketed formulation. The supremacy in the in vivo pharmacokinetic parameters of RLF-41 and RLF-48 was demonstrated with 3.33 and 3.50 times enhancement in the bioavailability of RLF with respect to RLF suspension. To sum up, the results obtained were superior and promising for synthesized nanoparticles and more precisely for MCM-48 amongst them.     

Quantitative measurement of a mixture of mesophases cubic MCM-48 and hexagonal MCM-41 by 13C CP/MAS NMR

The ¹³C CP/MAS NMR was used to quantify a mixture of cubic MCM-48 and hexagonal MCM-41 mesophases by means of interpretation of their surfactant organization, which cannot be determined by X-ray diffraction (XRD) techniques.     

不同偶联剂对介孔分子筛MCM-41的表面修饰及对MCM-41/环氧树脂性能的影响

使用2种硅烷偶联剂(KH550和KH792)对介孔分子筛MCM-41进行表面改性,采取氮气吸附-脱附、FTIR和TGA等进行表征,并采用原位聚合法制备了MCM-41/环氧树脂复合材料,研究了偶联剂种类和MCM-41用量等对复合材料固化过程及性能的影响。结果表明:硅烷偶联剂可与MCM-41表面的硅羟基反应,在分子筛内外表面接枝上功能化基团。经表面修饰的MCM-41比表面积下降为原来的1/5,KH550在MCM-41表面接枝率仅为KH792的一半。KH550与MCM-41外表面反应得更充分,KH792对MCM-41孔道内壁的修饰效果更强。固化动力学结果表明:KH792的功能化基团有伯胺和仲胺,与环氧树脂具有更高的反应活性,但不利于环氧大分子进入孔道,仅以球形粒子的形式添加在环氧树脂中;KH550表面修饰的MCM-41可使环氧大分子进入孔道内形成互穿结构。KH550表面修饰体系更多体现出MCM-41多孔的特征,形成了有机-无机互穿结构的复合体系,大幅度提高了储能模量和玻璃化转变温度。KH792表面修饰体系则呈常规球形纳米粒子的特征,其储能模量和玻璃化转变温度较纯环氧树脂有所提高但幅度不大。     

TiO2在MCM-41内表面单层及双层分散的结构表征

首次以有机物钛酸丁酯为前驱体,合成了ＴiO2呈单层分散状态（Ｔi/Si=0．２０）或双层分散状态（Ｔi/Si=0．39)的介孔分子筛ＭＣＭ－４１（Si/Al=35）,并以ＸＲＤ,ＦＴＩＲ,Ｎ２吸附－脱附,固体ＵＶ－vis漫反等表征手段对其结构特征的氧化钛分散状态进行了研究,结果表明：ＴiO2在介孔分子筛ＭＣＭ－４１孔道中分散,ＭＣＭ－４１骨架结构结晶度降低,但是附着二层ＴiO2后,仍能保持长程有序结构;ＴiO2与ＭＣＭ－４１骨架结构结果度降低低,但是附着二层ＴiO2后,仍能保持长程有序结构,ＴiO2与ＭＣＭ－４１孔道表面的ＳiO2比化学键连接,生成Ｓi-O-Ti键;无论是单层还是双层分散的ＴiO2在ＭＣＭ－４１内孔壁均匀分散,且由于ＴiO2粒子的减小使其对紫外光的吸收发生明显的蓝移现象。.     

Hollow MCM-41 microspheres derived from P(St-MMA)/MCM-41 core/shell composite particles

In soap-free latex media, poly(styrene-methyl methacrylate)/MCM-41 core/shell composite microspheres have been fabricated by adding silicate source in batches. In this process, silicate species and the surfactant micelles were self-assembled into 2-dimensional hexagonal arrangement on the surface of P(St-MMA) microspheres. Hollow MCM-41 microspheres were obtained via removing polymer core by solvent. XRD, TEM, IR and N₂ adsorption-desorption analysis were applied to characterize products. The results showed that average diameter and wall thickness of hollow MCM-41 microspheres is about 240 nm and 20 nm, respectively. Results of N₂ adsorption-desorption indicate that hollow MCM-41 microspheres possess a highly ordered mesoporous structure and a narrow pore distribution with a mean value of 2.34 nm.     

TiO_2在MCM-41内表面单层及双层分散的结构表征

首次以有机物钛酸丁酯为前驱体,合成了ＴｉＯ２呈单层分散状态（Ｔｉ／Ｓｉ＝０.２０）或双层分散状态（Ｔｉ／Ｓｉ＝０．３９）的介孔分子筛ＭＣＭ－４１（Ｓｉ／Ａｌ＝３５）,并以 ＸＲＤ,ＦＴＩＲ,Ｎ２吸附－脱附,固体ＵＶ－ｖｉｓ 漫反射等表征手段对其结构特征和氧化钛分散状态进行了研究．结果表明： ＴｉＯ２在介孔分子筛ＭＣＭ－４１孔道中分散, ＭＣＭ－４１骨架结构结晶度降低,但是附着二层ＴｉＯ２后,仍能保持长程有序结构; ＴｉＯ２与ＭＣＭ－４１孔道表面的ＳｉＯ２以化学键连接,生成Ｓｉ－Ｏ—Ｔｉ键;无论是单层还是双层分散的 ＴｉＯ２在 ＭＣＭ－４１内孔壁均匀分散;且由于ＴｉＯ２粒子的减小使其对紫外光的吸收发生明显的蓝移现象．     

硅烷修饰对环氧树脂/纳米介孔MCM-41复合材料性能的影响

用偶联剂将纳米介孔MCM-41粉体修饰后与环氧树脂溶液共混,制备出环氧树脂/MCM-41纳米复合材料.研究了偶联剂的含量和不同溶剂的修饰对纳米介孔MCM-41粉体分散性和复合材料力学性能的影响.结果表明,加入适量的偶联剂和在极性较小的介质中修饰,可制备出单分散的纳米介孔MCM-41颗粒增强的新型网络复合材料.偶联剂中的有机基团-(CH2)3-NH2不仅进入孔道、修饰了MCM-41的孔壁,而且使介孔分子筛保持了有序的孔道结构.环氧树脂高分子链与偶联修饰后的MCM-41颗粒的内、外表面以强烈的化学键结合,使MCM-41颗粒均匀分散在聚合物基体中,提高了材料的力学性能,其拉伸强度比基体树脂提高了69%,杨氏模量提高了90%.     

氟化MCM-41的制备及超声触发释药性能研究

采用微波法制备了MCM-41,并将其与NH4F反应制得氟化MCM-41(F-MCM-41),采用浸渍法将抗肿瘤药物5-氟尿嘧啶(5-FU)分别组装到MCM-41和氟化MCM-41中。采用XRD、FT-IR、低温N2吸附和TG对MCM-41、氟化MCM-41和药物组装体进行了表征,考察了常规条件和超声条件下组装体在人工模拟胃液中的药物释放行为。结果表明,药物组装体超声条件下的药物释放速率明显优于常规释放。     

Amine-impregnated MCM-41 in post-combustion CO2 capture: Synthesis,characterization, isotherm modelling

In this study, a composite mesoporous silica material MCM-41 (Mobil composite matter) is impregnated with monoethanolamine (MEA) as primary linear amine, benzylamine (BZA) as primary cyclic amine and N-(2-aminoethyl) ethanolamine (AEEA) as secondary diamine and the effects of amine loading, amine type, CO₂ partial pressure and adsorption temperatures on the CO₂ adsorption are investigated. The CO₂ adsorption performances of MCM-41 and amine impregnated MCM-41 samples are studied up to 1 bar of CO₂ partial pressure and the temperature range of 25–60 °C. The amine loadings (% impregnation) are optimized for maximum CO₂ uptake. The materials are characterised using N₂ adsorption/desorption isotherm, Fourier Transform Infrared (FT-IR) Spectroscopy, Thermogravimetric (TGA) and Elemental (CHNS) analysis. The materials have shown good structural and thermal stability. The MCM-41-40%AEEA, MCM-41-40%BZA and MCM-41-50%MEA samples are exhibited the CO₂ adsorption capacity of 2.34 mmol/g (102.98 mg/g), 0.908 mmol/g (39.96 mg/g) and 1.47 mmol/g (64.69 mg/g) respectively. The CO₂ uptake of MCM-41-40%AEEA is 3.5 times higher than that of in MCM-41 (0.68 mmol/g) and it is also the highest reported value as di-amine impregnated MCM-41. The results indicated that the adsorption capacities of the materials (MCM-41 and MCM-41-40%AEEA) are decreased with an increase of adsorption temperature in the range of 25–60 °C. The Freundlich, Langmuir, Sips and Toth isotherm models are used to correlate and predict experimental CO₂ adsorption data. The Sips and Toth isotherm models are found to be better fitted with the experimental data. The isosteric heat of adsorption of MCM-41 and MCM-41-40%AEEA samples are also calculated from Van’t Hoff plot using iSorbHP-win instrumental analysis software in the experimental temperature range.     

Functionalization of mesoporous MCM-41 for the delivery of curcumin as an anti-inflammatory therapy

In this study, mesoporous silica nanoparticles (MSNs) composed of MCM-41 were synthesized and modified with amine groups (i.e., NH₂) to form NH_2/MCM-41, which was loaded with curcumin (CUR) to form CUR@NH₂/MCM-41 to create an efficient carriers in drug delivery systems (DDSs). The three samples (i.e., pure MCM-41, NH₂/MCM-41, and CUR@NH₂/MCM-41) were characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transition electron microscopy (TEM), and a thermogravimetric analyzer (TGA). The study investigated the effect of the carrier dose, CUR concentration, pH, and contact time on the drug loading efficiency (DLE%) by adsorption. The best DLE% for MCM-41 and NH₂/MCM-41 was found to be 15.78 and 80%, respectively. This data demonstrated that the Langmuir isotherm had a greater correlation coefficient (R²) of 0.9840 for MCM-41 and 0.9666 for NH₂/MCM-41 than the Freundlich and Temkin isotherm models. A pseudo-second-order kinetic model seems to fit well with R² = 0.9741 for MCM-41 and R² = 0.9977 for NH₂/MCM-41. A phosphate buffer solution (PBS) with a pH of 7.4 was utilized to study CUR release behavior. As a result, the full release after 72 h was found to have a maximum of 74.1% and 29.95% for pure MCM-41 and NH₂/MCM-41, respectively. The first-order, Weibull, Hixson-Crowell, Korsmeyer-Peppas, and Higuchi kinetic release models were applied to releasing CUR from CUR@MCM-41 and CUR@NH₂/MCM-41. The Weibull kinetic model fit well, with R² = 0.944 and 0.96912 for pure MCM-41 and NH₂/MCM-41, respectively.     

磁性MCM-41分离回收RT培司废水中四甲基氢氧化铵的研究

硝基苯法合成RT培司(4-氨基二苯胺)的废水色度高、组分复杂、催化剂四甲基氢氧化铵(TMAOH)难以分离回收。提出采用磁性MCM-41对RT培司废水中有机副产物进行选择性吸附分离。制备的磁性MCM-41样品采用X射线衍射仪(XRD)、透射电子显微镜(TEM)、扫描电子显微镜(SEM)、N₂吸附-脱附和振动样品磁场计(VSM) 等手段进行表征。结果表明, 磁性MCM-41颗粒的粒径范围为200~300 nm, BET比表面积约为655.2 m²/g, 孔径分布为0.5~4 nm, 内核铁酸镍的存在使磁性MCM-41具有超顺磁性。吸附研究表明磁性MCM-41对RT培司废水中吩嗪、偶氮苯和苯胺等有机物具有良好吸附作用, 经5次吸附磁分离后, RT培司废水中四甲基氢氧化铵能够达到回用要求, 吸附后的磁性MCM-41在外加磁场下极易分离。     

资源化利用铁尾矿制备全硅介孔分子筛MCM-41

以鞍山铁尾矿为硅源,CTAB为模板剂,采用水热合成法合成出全硅介孔分子筛MCM-41。采用X射线衍射分析研究了pH值、CTAB与SiO2配比、晶化温度和晶化时间对MCM-41结构的影响,结果表明MCM-41的合成条件为n（CTAB）/n（SiO2）=0.05～0.60,pH值=8～11,晶化时间〉24h,晶化温度60～100℃。TEM可观察到样品具有典型的按六方对称性排列的孔道结构,孔径在2～4nm变化。FT-IR证明了分子筛具有硅氧四面体骨架。     

MoO3在介孔分子筛MCM-41上分散和存在状态的研究

在773K加热MoO₃和MCM-41的机械混合物,可以实现 MoO₃分散在介孔分子筛MCM-41表面,用透射电镜和选区电子衍射,配合XRD和液氮温度下氮吸附-脱附曲线和BJH孔径分布,研究了活性组分MoO₃在有序介孔材料MCM-41上的存在状态,以及MoO₃分散到MCM-41表面后MCM-41的结构变化情况.结果表明:当MoO₃的含量小于单层分散阈值,加热后MoO₃的XRD衍射峰彻底消失;用HRTEM观察不到分散在MCM-41表面或孔道中的MoO₃颗粒,而EDS能谱证明在MCM-41的孔道中有呈分散态的MoO₃存在.MoO₃的含量大于单层分散阈值,通过加热不能使MoO₃完全分散在MCM-41表面,而且XRD、HRTEM、氮吸附-脱附等温线和孔径分布都表明由于MoO₃的分散量较大,载体MCM-41的有序介孔结构遭到破坏.     

MCM-41 填加量与偶联修饰对复合材料拉伸性能的影响

通过溶液共混法制备出MCM-41/ 环氧树脂、偶联修饰MCM-41/ 环氧树脂纳米复合材料。研究了填充MCM-41 介孔分子筛颗粒的偶联修饰以及不同的填充颗粒含量对分散性和复合材料拉伸性能的影响。结果表明: 在MCM-41/ 环氧树脂纳米复合材料中, MCM-41 仍保持着长程有序的孔道结构。修饰后的MCM-41 变成亲油性, 有利于增强颗粒与环氧树脂间的界面结合和纳米网络结构的形成, 使MCM-41 颗粒更能均匀分散在聚合物基体中, 提高复合材料的拉伸性能。修饰后的MCM-41 填加量为2.5 %(质量分数) 时, 拉伸强度达到最大值,比基体树脂提高99.2 % , 杨氏模量提高了110 %。      

温和条件下介孔分子筛MCM-41的修饰与表征

在温和条件下,以３－氨丙基三乙氧基硅烷为偶联剂,修饰介孔分子筛 ＭＣＭ－４１（Ｓｉ／Ａｌ＝３５）,成功地将有机官能团引入到介孔分子筛孔道中,制备了一种无机一有机复合材料ＭＣＭ－（ＣＨ_２）_３ＮＨ_２,以 ＸＲＤ、ＦＴＩＲ、ＤＴＡ－ＴＧＡ、 Ｎ_２吸附－脱附和 ＨＲＥＭ表征了复合材料;结果表明：有机基团－（ＣＨ_２）_３ＮＨ_２不仅进人孔道、修饰了ＭＣＭ－４１的孔壁,而且使介孔分子筛ＭＣＭ－４１保持了有序的孔道结构．     

MoO3在介孔分子筛MCM-41上分散和存在状态的研究

在773K加热MoO3和MCM－41的机械混合物，可以实现MoO3分散在介孔分子筛MCM－41表面，用透射电镜和选区电子衍射，配合XRD和液氮温度下氮吸附－脱附曲线和BJH孔径分布，研究了活性组分MoO3在有序介 材料MCM－41上的存在状态，以及MoO3分散到MCM－41表面后MCM－41的结构变化情况。结果表明：当MoO3的含量小于单层分散阈值，加热后MoO3的XRD衍射峰彻底消失，用HRTEM观察不到分散在MCM－41表面或孔道中的MoO3颗粒，而EDS能谱证明在MCM－41的孔道中有呈分散态的MoO3存在。MoO3的含量大于单层分散阈值，通过加热不能使MoO3完全分散在MCM－41表面，而且XRD、HRTEM、氮吸附－脱附等温线和孔径分布都表明由于MoO3的分散量较大，载体MCM－41的有序介孔结构遭到破坏。     

SiC-dopped MCM-41 materials with enhanced thermal and hydrothermal stabilities

SiC-dopped MCM-41 mesoporous materials were synthesized by the in situ hydrothermal synthesis, in which a small amount of SiC was added in the precursor solvent of molecular sieve before the hydrothermal treatment. The materials were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, N₂ physical adsorption and thermogravimetric analysis, respectively. The results show that the thermal and hydrothermal stabilities of MCM-41 materials can be improved obviously by incorporating a small amount of SiC. The structure collapse temperature of SiC-dopped MCM-41 materials is 100 °C higher than that of pure MCM-41 according to the differential scanning calorimetry analysis. Hydrothermal treatment experiments also show that the pure MCM-41 will losses it's ordered mesoporous structure in boiling water for 24 h while the SiC-dopped MCM-41 materials still keep partial porous structure.