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.     

Effect of amine and carboxyl functionalization of sub-micrometric MCM-41 spheres on controlled release of cisplatin

Mesoporous MCM-41 type silica spheres having a sub-micrometer size were synthesized following an adaptation of Stöber's method. This parent material was then functionalized with 3-aminopropyl triethoxysilane and with 3-propanonitrile triethoxysilane, followed by oxidation of the cyano-group to the corresponding carboxy-group. After proper characterization, the samples were loaded with cisplatin and subjected to in vitro tests in order to obtain the corresponding drug release profile. The carboxy-functionalized MCM-41 sample was found to show a release kinetics that should facilitate controlled drug delivery over a significantly larger time period (about 140 h) than both, unmodified MCM-41 and amino-functionalized MCM-41 samples.     

Adsorption and release of biocides with mesoporous silica nanoparticles

In this proof-of-concept study, an agricultural biocide (imidacloprid) was effectively loaded into the mesoporous silica nanoparticles (MSNs) with different pore sizes, morphologies and mesoporous structures for termite control. This resulted in nanoparticles with a large surface area, tunable pore diameter and small particle size, which are ideal carriers for adsorption and controlled release of imidacloprid. The effect of pore size, surface area and mesoporous structure on uptake and release of imidacloprid was systematically studied. It was found that the adsorption amount and release profile of imidacloprid were dependent on the type of mesoporous structure and surface area of particles. Specifically, MCM-48 type mesoporous silica nanoparticles with a three dimensional (3D) open network structure and high surface area displayed the highest adsorption capacity compared to other types of silica nanoparticles. Release of imidacloprid from these nanoparticles was found to be controlled over 48 hours. Finally, in vivo laboratory testing on termite control proved the efficacy of these nanoparticles as delivery carriers for biopesticides. We believe that the present study will contribute to the design of more effective controlled and targeted delivery for other biomolecules.     

A novel self-assembly approach to form tubular poly(diphenylamine) inside the mesoporous silica

MCM-41 materials were synthesized using alkyl(decosane, dodecyl)trimethyl ammonium bromide as structure directing surfactants. X-ray diffraction (XRD) analysis and nitrogen adsorption measurements reveal that the pores are hexagonal with tunable textural properties through the choice of surfactant and experimental condition. Poly(diphenylamine), PDPA was entrapped into the pores of MCM-41 by initial sorption of diphenylamine (DPA, monomer) in a medium (napthalein sulfonic acid) that provides self-assembling of DPA inside the pores and subsequent oxidative of polymerization with peroxydisulphate. Clear presence of an additional peak (around 9-10°) in XRD pattern for the DPA loaded MCM-41 provides evidence for self-assembled structure. Upon polymerization the self-assembly of DPA molecules resulted tubular PDPA inside the pores of MCM-41. PDPA thus formed shows different electronic property than the PDPA prepared by conventional method. XRD and FTIR spectroscopic analysis of PDPA loaded MCM-41 clearly informs that PDPA are entrapped in channels of MCM-41.     

pH及温度双重敏感性MCM-41/P(AA-co-NIPAAm)的制备和释药性能

通过微波辅助水热法制备了介孔分子筛 MCM-41,并将其与N-异丙基丙烯酰胺(NIPAAm)和丙烯酸(AA)原位聚合生成了一种新型的pH及温度双重敏感型复合材料MCM-41/P(AA-co-NIPAAm),用XRD、N₂吸附-脱附、FT-IR、TGA对所得材料进行表征,结果表明合成了一种新型的复合材料。以氢氯噻嗪为模型药物进行载药性能测试并考察了此释药系统在不同pH及温度环境中的敏感释药行为。结果显示：MCM-41/P(AA-co-NIPAAm)复合材料的载药量达45.8%,并且通过改变环境体系的pH及温度可以有效控制药物的释放。复合材料在肠道靶向给药方面有一定的应用潜力。     

Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant

Two different types of ordered mesoporous nanoparticles, namely MCM-41 and MCM-48, with similar pore sizes but different pore connectivity, were loaded with aprepitant via a passive diffusion method. The percentage of the loaded active agent, along with the encapsulation efficiency, was evaluated using High-performance Liquid Chromatography (HPLC) analysis complemented by Thermogravimetric Analysis (TGA). The determination of the pore properties of the mesoporous particles before and after the drug loading revealed the presence of confined aprepitant in the pore structure of the particles, while Powder X-ray Diffractometry(pXRD), Differential Scanning Calorimetry (DSC), and FTIR experiments indicated that the drug is in an amorphous state. The release profiles of the drug from the two different mesoporous materials were studied in various release media and revealed an aprepitant release up to 45% when sink conditions are applied. The cytocompatibility of the silica nanoparticles was assessed in Caco-2 cell monolayers, in the presence and absence of the active agent, suggesting that they can be used as carriers of aprepitant without presenting any toxicity in vitro.     

改性介孔分子筛对布洛芬的吸附与控制释放

采用合成后改性将氨基嫁接进介孔MCM41和SBA-15孔道内,对功能化的2种分子筛进行药物吸附与控制释放的研究。利用红外光谱仪(IR)、智能重量分析仪(IGA)等表征手段对吸附剂的物理结构和化学组成进行表征。对药物布洛芬(IBU)的吸附量进行比较,结果表明,氨基改性的MCM41(MCM41-NH2)对布洛芬的吸附性能大...     

含铁MCM-41的合成与表征

实验采用液相沉积方式,向MCM-41有序介孔微球的介孔中引入铁盐,通过加热使铁盐分解,铁以氧化物纳米颗粒或Fe-O纳米团簇的形式存在于有序介孔微球的介孔中,从而获得含铁MCM-41有序介孔微球.对不同铁含量的MCM-41进行了比较性表征,并研究了不同铁源对含铁MCM-41合成的影响.研究表明,以Fe(acac)₃的甲苯溶液和Fe(NO₃)₃的水溶液为铁源时,所得试样中铁的含量均随铁离子浓度的增大而增大.铁离子浓度相同时,由前者所得试样的载铁量是后者的3～4倍,最大铁负载量达1 mmol•g^-1.载铁后,有序介孔微球的比表面积、孔容和孔径均减小.以Fe(NO₃)₃的水溶液为铁源时,载铁前驱体试样煅烧后,MCM-41的硅氧骨架发生收缩,而以Fe(acac)₃的甲苯溶液为铁源时,MCM-41的硅氧骨架未见变化.因此,从载铁量及负载过程对有序介孔材料骨架结构的影响看,Fe(acac)₃的甲苯溶液作为铁源用于合成含铁MCM-41优于Fe(NO₃)₃的水溶液.     

Synthesis of a highly hydrophobic silica mesostructure by a modified co-condensation procedure and evaluation of its drug release capability

A highly hydrophobic silica mesostructure was synthesized by a modification on the conventional co-condensation procedure that involved the partial substitution of hexadecytltrimethylammonium, used as mesostructure directing agent, by hexadecyltrimethoxysilane. That modification allowed the production of a highly ordered hexagonal silica mesostructure with the mesopores partially filled with high amounts of hexadecyl chains, covalently bonded to inorganic framework. After extracting the reminiscent template molecules, ibuprofen was loaded into the mesostructure in order to evaluate its drug release properties. The drug loading amount (21 wt%) was comparable to the one reported for MCM-41 with grafted propylamine groups (25 wt%), indicating that C₁₆-chains were not fully compacted occluding the pores. A slow ibuprofen release was observed in simulated body fluid (pH 7.2) by a process controlled by an anomalous transport with contribution of diffusional and relaxational components, according to the Korsmeyer-Peppas kinetics model. That hydrophobic mesostructure produced has the potential of being use as a carrier for low water soluble drugs with an extended delivery effect, but without the disadvantages of co-releasing toxic surfactant molecules or the need of non-toxic specific templates to be prepared.     

Three Different Interaction Patterns between MCM-41 and Proteins

As one of the most studied mesoporous silica nanoparticles (MSNs) in drug delivery systems, Mobil Composition of Matter No. 41 (MCM-41) possesses unique properties including perfect channel architecture, excellent load capacity, and good biocompatibility. However, the applications of MCM-41 nanoparticles in drug delivery have not yet been industrialized, due to the interaction between MCM-41 and biomolecules (especially proteins) that affect their in vivo behaviors after dosing. To investigate the interactions between MCM-41 and proteins, this study selected bovine serum albumin (BSA), lysozyme (Lyso), and bovine hemoglobin (BHb) as model proteins and characterized the ultraviolet-visible, fluorescence, circular dichroism spectra and the protein adsorption of MCM-41-protein complex. The UV-Vis spectra exhibited the different absorption increment degrees of three proteins. The fluorescence spectra showed that the fluorescence intensity of proteins changed by different trends. The CD spectra indicated that the secondary structure changes were ranked as BSA > Lyso > BHb, which is consistent with the protein’s adsorption capability on MCM-41. It was shown that there were three different patterns of MCM-41-proteins interactions. The hydrophilic and low-charged BSA followed the strong interaction pattern, the hydrophilic but heavily charged Lyso followed the moderate interaction pattern, and the hydrophobic BHb followed the weak interaction pattern. Different interaction patterns would lead to different effects on the structural properties of proteins, the surface chemistry of MCM-41, and the absorption capability of proteins on MCM-41. We believe our study will provide a better insight into the application of MCM-41 nanoparticles in drug delivery systems.     

PEI-MCM-41吸附剂的制备及其CO_2吸附性能研究

使用不同方法合成了MCM-41,制备出具有不同骨架结构和内部孔道结构的介孔分子筛。通过XRD、高倍投射电镜、低温氮吸附/脱附等方法对样品进行了表征分析。用PEI对MCM-41分子筛进行改性,然后使用热重方法测定了其对CO2的吸附量。结果表明,使用硅酸钠和硫酸为原料制备的样品具有较大的比表面积和孔容,在该样品上负载50%PEI吸附量达到了269.3 mg/g,是同等条件下单纯PEI吸附量的3.4倍。说明将PEI负载在具有大比表面积和孔容的MCM-41介孔分子筛上,可以使PEI得到充分分散,并充分利用PEI分子上的氨基。     

In-vitro drug release kinetics studies of mesoporous SBA-15-azathioprine composite

The mesoporous silica (or SBA-15) was loaded with azathioprine drug. Azathioprine drug was incorporated into mesoporous silica by post impregnation method to reduce its toxic effects by controlling the drug release property. The synthesized pure SBA-15 and SBA-15-azathioprine composite were characterized by UV–visible spectrophotometry, thermo-gravimetric analysis, small and large angle powder X-ray diffraction, field emission scanning electron microscopy, high resolution transmission electron microscopy, Fourier transform infrared spectroscopy and nitrogen adsorption–desorption analysis. The successful inclusion of azathioprine drug in host material SBA-15 was confirmed by the reduced surface area (114 m²/g) and pore diameter (6.5 nm) of the organic–inorganic composite material. The drug entrapment efficiency of 90.67 % and loading efficiency of 72.67 % was achieved. The azathioprine drug release process from the mesoporous silica to simulated gastric, intestinal and body fluid were examined and the controlled release effect of the azathioprine drug in all fluids were studied. The Korsmeyer–Peppas model fits well the drug release data with the non-Fickian diffusion model and zero order kinetics for produced mesoporous silica. The controlled drug release enhanced the bioavailability and reduces its repeated administration. Hence, the composite drug can reduce the toxicity and side effects of the azathioprine.     

Pyrolysis of Polyethylene over Aluminum-Incorporated MCM-41 Catalyst

Aluminum-containing MCM-41 catalysts were synthesized in this study by impregnation of aluminum into hydrothermally synthesized MCM-41. Aluminum was loaded into the porous framework of silica with different Al/Si ratios, using aluminum isopropoxide as the aluminum source. These catalysts exhibited Type IV adsorption–desorption isotherms and had a pore diameter of 2.4 nm. Aluminum species were coordinated tetra- and octahedrally in the structure of catalysts. Diffuse Reflectance Fourier Transform Infrared Spectra (DRIFTS) analysis of the pyridine-adsorbed catalysts revealed the existence of Brönsted acid sites in the synthesized catalysts in addition to the Lewis acid sites. The performance of these catalysts was tested in the degradation of polyethylene using a thermogravimetric analyzer. Pure MCM-41 did not show a significant reduction in the degradation temperature of polyethylene, whereas aluminum-impregnated catalysts were successful in decreasing the temperature.     

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.     

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.     

席夫碱锌改性介孔硅对毒死蜱的吸附与缓释

以3-氨丙基三乙氧基硅烷（APTES）、水杨醛和锌离子为改性剂,通过共缩聚法合成席夫碱锌配合物改性MCM-41（Zn-MCM-41）,并以毒死蜱为模型药物,制备了毒死蜱/席夫碱锌配合物改性MCM-41缓释体系。利用XRD、N₂吸附-脱附、FTIR、DSC和XPS对MCM-41、氨基改性MCM-41（NH₂-MCM-41）、水杨醛席夫碱改性MCM-41（SA-MCM-41）的结构、毒死蜱的分布形态和Zn-MCM-41的配位情况进行了表征,考察了MCM-41在改性前后对毒死蜱的吸附量,并着重探究了其对毒死蜱的吸附动力学、吸附热力学以及缓释性能。结果表明,APTES和水杨醛席夫碱改性后的MCM-41仍具有较为有序的介孔结构。MCM-41对毒死蜱的吸附量为54 mg·g^-1,Zn-MCM-41的吸附量为186 mg·g^-1,相对于MCM-41,其吸附量增加了244%。改性前后的MCM-41对毒死蜱的吸附动力学和吸附热力学分别符合准一级动力学模型和Freundlich模型。毒死蜱/席夫碱锌配合物改性MCM-41缓释体系的释药行为可用Riger-Peppas动力学模型来描述,其药物释放由Fick扩散控制。     

Separation and Recovery of Tetramethyl Ammonium Hydroxide with Mesoporous Silica Having a Hexagonal Structure (MCM-41)

Separation and recovery of tetramethyl ammonium hydroxide (TMAH) was investigated using several types of MCM-41 (mesoporous silica having hexagonal structure) adsorbents. The MCM-41s were prepared by hydrothermal synthesis with structure-directing agents with different alkyl chains. The prepared MCM-41s were characterized with X-ray diffraction, transmission electron microscope, nitrogen gas adsorption, and zeta potential, and then used for adsorption of TMAH. The adsorption of TMAH with MCM-41s increased with pH up to pH ≈ 10 and then decreased as the MCM-41 dissolved. The adsorption of TMAH progressed via the Langmuir mechanism. The maximum adsorption corresponded to the pore diameter and the pore volume of the MCM-41s. MCM-41 also possesses selectivity for TMAH against phenol. The chromatographic operation was conducted using granulated MCM-41 to avoid excessive pressure-drop through the packed column and quantitative adsorption-elution processing of TMAH could be achieved.     

MCM-41 for furosemide dissolution improvement

The ordered mesoporous silica material MCM-41 was used to prepare a novel drug delivery system (DDS) for oral administration of the diuretic furosemide (FURO), labeled in class IV of the Biopharmaceutics Classification System (BCS). This drug is characterized by both low solubility and permeability and its absorption window is the stomach and the proximal small intestine. Thus, the aim of this work was the development of an immediate formulation that could improve the drug release in its preferential absorptive regions.Three inclusion products MCM-41-FURO-E/D, MCM-41-FURO-S and MCM-41-FURO-E have been prepared in three different ways in order to find the best preparation conditions. They were characterized by XRPD, DSC, FT-IR, TGA and B.E.T. and then the inclusion products displaying the best characteristics were submitted to in vitro studies. They evidenced that the examined inclusion products displayed FURO dissolution enhancement, followed by a complete release within 90 min. Moreover, physical stability studies revealed that MCM-41 is able to stabilize the drug preventing it from re-crystallization. At last, as FURO is light sensitive, the effect of MCM-41 on drug photochemical stability was also investigated and the results indicated the protective action exerted by the matrix.     

CONFINEMENT EFFECTS ON ADSORPTION AND DIFFUSION OF HEXANE IN NANOPOROUS MCM-41 WITH DIFFERENT PORE SIZES: A MOLECULAR DYNAMICS STUDY

We report the results of molecular dynamics (MD) simulations using a new semi-empirical intermolecular interaction potential on the adsorption and diffusion of hexane in siliceous MCM-41 at 300 K. The potential function is tuned to give an adsorption energy of ? 9.1 kcal/mol, reproducing the experimental value for a corresponding pore size. We investigated MCM-41 models with four different pore sizes and studied loadings from one molecule of hexane up to a loading corresponding to the density of liquid hexane. As a result of confinement in MCM-41, the free energy of adsorption of hexane increases when the pore sizes decrease; for example, the adsorption energy increases from ? 9.1 to 13.7 kcal/mol for the largest to the smallest pore size for a loading of one molecule. Also, the adsorption energy increases by 3–4 kcal/mol for all pore sizes when the loading is increased from one hexane molecule to the density of liquid hexane. The calculated self-diffusion coefficients of hexane in MCM-41 with a pore diameter of 27 Å are in the order of 1 × 10^?5 cm²/s, depending on the loading, which is in reasonable agreement with available experimental data. The self-diffusion coefficients decrease with increasing loadings and when the pore sizes decrease. The average distance between the centers of the mass of hexane molecules in the smallest pores is only marginally less than in the larger pores and in the liquid phase. For low loadings the hexane molecules lie parallel to the pore channel for every pore size. When the loading is increased, they build up concentric rings. These rings of hexane molecules are less well separated from each other in the larger models, and thus their structure more resembles the liquid phase.     

聚噻吩/MCM-41的合成与表征

文章以FeCl3为氧化剂,采用原位化学聚合的方法制备了聚噻吩/MCM-41新型复合材料,并对其结构和性能进行了表征。结果表明:小角X射线衍射和氮气吸附与脱附说明复合材料具有规则的介孔结构并且孔径明显小于分子筛MCM-41的孔径,红外光谱分析进一步证明PT进入了MCM-41的介孔孔道内,热重分析表明,聚噻吩进入孔道之后热稳定性得到了提高。