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。     

右旋布洛芬/尿素改性蒙脱土复合物的制备及体外释药性能

以蒙脱土为药物载体,利用尿素固相研磨法将蒙脱土层间距撑大,以提高其载药量;采用溶液插层法实现右旋布洛芬的有效负载,制备右旋布洛芬/尿素改性蒙脱土[S（+）-IBU/urea-MMT]复合物;借助X射线衍射（XRD）和傅里叶红外变换光谱（FT-IR）对复合物进行结构表征;采用透析法研究复合物中药物的体外释药性能;运用3种数学模型对其体外释放行为进行拟合分析,探索释药机理。结果表明,在尿素的作用下,蒙脱土的层间距由1.20 nm增大到1.79 nm,右旋布洛芬的负载量最高可达227.9 mg·g^-1,较改性前提高了30%;S（+）-IBU/urea-MMT复合物具有良好的缓释效果,在人工模拟胃液（pH 1.2）和人工模拟肠液（pH 6.8）中的累计释放量分别为19.2%和88.4%;复合物的释药行为基本符合零级释放动力学模型。     

pH响应性PAA/毒死蜱/氨基化介孔硅缓释体系的制备与性能

以共缩聚法合成氨基化介孔硅,采用浸渍法制备毒死蜱/氨基化介孔硅,并以带负电荷的聚丙烯酸（PAA）为功能分子,通过静电吸附作用制备了具有pH响应的PAA/毒死蜱/氨基化介孔硅缓释体系。利用XRD、N₂吸附-脱附、TEM、SEM、TG、Zeta电位和FTIR对PAA/毒死蜱/氨基化介孔硅的结构进行了表征,并探究了其在不同pH和温度下的释药行为。结果表明,PAA通过静电作用包覆于毒死蜱/氨基化介孔硅的表面。缓释体系的药物释放主要受到PAA的阻碍作用,PAA修饰载药氨基化介孔硅显示出明显的pH响应性,当pH≤7时,其药物释放速率随pH减小而增大,而在偏碱性条件下的释药速率稍大于中性环境。同时,载药体系的释药速率还受到温度的影响。其释药行为可用Korsmeryer-Pappas动力学模型来描述。     

负载盐酸阿霉素交联透明质酸的缓释性能

以抗癌药物盐酸阿霉素为模型,交联透明质酸为载体,通过溶胀作用吸附药物分子,再冷冻干燥、碾压成形,制备了一系列具有不同载药量和一定缓释效果的载药交联透明质酸膜。通过SEM观测其微结构,利用紫外分光光度法检测其药物体外释放行为,并研究不同释放时间、载药量和透明质酸酶对药物释放行为的影响。结果表明,12h内药物释放较快,随后释放平缓,药物累积释放速度与载药量呈反比;加入透明质酸酶后,由于交联透明质酸的不断降解,药物累积释放速度比无透明质酸酶时快。     

羧甲基壳聚糖-蓖麻油基聚氨酯农药缓释微球的制备及性能

以羧甲基壳聚糖（CMCS）、蓖麻油（CO）和异佛尔酮二异氰酸酯（IPDI）为原料,自乳化法制备了羧甲基壳聚糖-蓖麻油基聚氨酯微球（CO-CMCS-PU）,通过分子自组装法负载阿维菌素（AVM）得到载药微球（CO-CMCS-PU@AVM）。采用FTIR、1HNMR、SEM、TGA等对产品结构及形貌进行表征,并探究了不同药量载药微球的包封率、缓释性能、抗紫外性能、叶面接触角和黏附性能。结果表明,相比AVM分散液,紫外照射后载药微球中AVM的保留率提高到43%,说明CO-CMCS-PU载体的抗紫外性能良好;载药微球比AVM分散液在黄瓜叶面上的接触角降低了20%以上,滞留量提高了40%以上,说明其在叶面上有较好的黏附性和润湿性;载药微球包封率可达80%以上,具有良好的缓释和pH响应释放性能,释药行为符合First-order动力学模型,药物释放受Fickian扩散控制。     

紫杉醇-SIBS体外药物释放动力学研究

采用聚（苯乙烯-b-异丁烯-b－苯乙烯）三嵌段共聚物（SIPS）作为紫杉醇药物载体,研究了紫杉醇释放动力学行为。对紫杉醇-SILKS载药共聚物进行了差示量热扫描仪分析（DSC）和原子力显微镜（AFM）的表征;研究了不同苯乙烯（St）含量的紫杉醇-SIBS载药共聚物在pH=7．4磷酸缓冲液（PBS）（37℃）中的动力学。结果表明紫杉醇-SIRS载药共聚物随着St含量的增加,紫杉醇的释放率较低,且其释药率在8d以后趋于平稳;在体外释药过程中随着磷酸缓冲液的置换量越大,紫杉醇的释放率越高。     

层状纳米羟基磷灰石/茶氨酸药物释药性能研究

本文以层状纳米羟基磷灰石为载体制备了羟基磷灰石/茶氨酸药物,并对其体外释药性能进行了初步研究.羟基磷灰石/茶氨酸药物在起始阶段具有很快的药物释放速率,50 min时的累积释放量接近80％,最终的释药量可达90％以上.而且在释药初期,载药量高的样品比载药量低的样品具有更高的累积释药百分量.     

啶虫脒/希夫碱改性凹凸棒土缓释体系的制备与性能

采用后接枝方法制备希夫碱铜离子配合物改性凹凸棒土（Cu2 -Sal-ATP）,采用浸渍法制备啶虫脒/凹凸棒土（ATP）缓释体系。利用FTIR、XRD、N2吸附-脱附、SEM和DSC 对改性凹凸棒土的结构进行了表征,并探究了改性凹凸棒土对农药啶虫脒的吸附行为和缓释体系的释药行为。结果表明,啶虫脒是以非晶相存在于改性凹凸棒土中,药物装载未改变载体的结构。有机改性提高了凹凸棒土对药物的载药量,且经希夫碱铜离子配位改性体系的载药量最高,其吸附行为符合准二级动力学模型。希夫碱铜离子配位改性凹凸棒土载药体系的缓释效果优于相应的希夫碱改性凹凸棒土（Sal-ATP）体系,载药体系的释药行为可用Korsmeryer-Pappas动力学模型来描述。     

N-mPEG-O-季铵化壳聚糖微球的制备及其载药性能

将聚乙二醇单甲醚（mPEG）醛化改性后,通过西佛碱反应接枝到自制的O-季铵化壳聚糖的NH2上,硼氢化钠还原制得N-mPEG接枝O-季铵化壳聚糖（QACS-mPEG）,反相悬浮法制备二乙烯基砜交联QACS-mPEG微球。用FTIR、1 H NMR、EA和SEM对产物进行表征,并且以酮洛芬为模型药物研究微球的载药性能及释放行为。结果表明,mPEG和季铵盐基团的引入提高了N-mPEG-O-季铵化壳聚糖微球的载药量,为4.31mg/mg;载药N-mPEG-O-季铵化壳聚糖微球在模拟肠液的缓释效果优于胃液,微球释药具有pH响应性。     

低临界胶束浓度PEGMA-b-PCL的制备及其 药物缓释性能

以ε-己内酯（ε-CL）为疏水链段,聚乙二醇甲醚甲基丙烯酸酯（PEGMA）为亲水链段,4-氰基-4-[(十二烷基硫基硫羰基)硫基]戊酸（CDPA）为可逆加成-断裂链转移（RAFT）试剂,在以甲苯为溶剂、N2氛围、80 ℃、反应24 h的条件下,通过RAFT聚合法制备了两嵌段聚合物PEGMA-b-PCL。将其自组装为胶束用作纳米药物载体,并以姜黄素（Cur）为胶束负载药物。考察了两嵌段聚合物结构、分子量及分布,表征了胶束载体粒径、形貌,测试了胶束载体的载药和释药性能。结果表明,不同嵌段聚合物相对分子质量范围为478~7318,此类聚合物具有较低的临界胶束浓度（CMC）,在常规条件下（pH=7.4）其范围为0.920~1.600 μg/mL。胶束载体粒径范围为:68.34~186.30 nm。当n(CDPA)∶n(ε-CL)=1∶200时,胶束载药量和包封率最高,可达12.05%和75.26%。在不同pH值环境下,药物缓释性能可达15 d,其中pH=5.0时释药量可达35.38%。     

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.     

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.     

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.     

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.     

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。     

Description of Release Process of Doxorubicin from Modified Carbon Nanotubes

The article discusses the release process of doxorubicin hydrochloride (DOX) from multi-wall carbon nanotubes (MWCNTs). The studies described a probable mechanism of release and actions between the surface of functionalized MWCNTs and anticancer drugs. The surface of carbon nanotubes (CNTs) has been modified via treatment in nitric acid to optimize the adsorption and release process. The modification efficiency and physicochemical properties of the MWCNTs+DOX system were analyzed by using SEM, TEM, EDS, FTIR, Raman Spectroscopy and UV-Vis methods. Based on computer simulations at pH 7.4 and the experiment at pH 5.4, the kinetics and the mechanism of DOX release from MWNT were discussed. It has been experimentally observed that the acidic pH (5.4) is appropriate for the efficient release of the drug from CNTs. It was noted that under acidic pH conditions, which is typical for the tumour microenvironment almost 90% of the drug was released in a relatively short time. The kinetics models based on different mathematical functions were used to describe the release mechanism of drugs from MWCNTs. Our studies indicated that the best fit of experimental kinetic curves of release has been observed for the Power-law model and the fitted parameters suggest that the drug release mechanism of DOX from MWCNTs is controlled by Fickian diffusion. Molecular dynamics simulations, on the other hand, have shown that in a neutral pH solution, which is close to the blood pH, the release process does not occur keeping the aggregation level constant. The presented studies have shown that MWCNTs are promising carriers of anticancer drugs that, depending on the surface modification, can exhibit different adsorption mechanisms and release.