Functionalized SBA-15 materials as carriers for controlled drug delivery: influence of surface properties on matrix-drug interactions

Mesoporous SBA-15 materials were functionalized with amine groups through postsynthesis and one-pot synthesis, and the resulting functionalized materials were investigated as matrixes for controlled drug delivery. The materials were characterized by FTIR, N(2) adsorption/desorption analysis, zeta potential measurement, XRD, XPS, and TEM. Ibuprofen (IBU) and bovine serum albumin (BSA) were selected as model drugs and loaded onto the unmodified and functionalized SBA-15. It was revealed that the adsorption capacities and release behaviors of these model drugs were highly dependent on the different surface properties of SBA-15 materials. The release rate of IBU from SBA-15 functionalized by postsynthesis is found to be effectively controlled as compared to that from pure SBA-15 and SBA-15 functionalized by one-pot synthesis due to the ionic interaction between carboxyl groups in IBU and amine groups on the surface of SBA-15. However, SBA-15 functionalized by one-pot synthesis is found to be more favorable for the adsorption and release of BSA due to the balance of electrostatic interaction and hydrophilic interaction between BSA and the functionalized SBA-15 matrix.     

pH值响应性毒死蜱/铜席夫碱配合物改性SBA-15的制备及缓释性能

以3-氨丙基三乙氧基硅烷（APTES）、水杨醛和铜离子为改性剂,通过后嫁接法制得铜席夫碱配合物改性SBA-15（Cu-SBA-15）,并以毒死蜱为模型药物,制备了毒死蜱/铜席夫碱配合物改性SBA-15缓释体系。利用TEM、SEM、XRD、N₂吸附-脱附、TG、FTIR和XPS对SBA-15、氨基改性SBA-15（NH₂-SBA-15）、水杨醛希夫碱改性SBA-15（SA-SBA-15）的形貌、结构和Cu-SBA-15的配位情况进行了表征,考察了SBA-15在改性前后对毒死蜱的吸附量和缓释性能,并着重探究了毒死蜱/铜席夫碱配合物改性SBA-15载药体系在不同pH值下的释药行为。结果表明,APTES和水杨醛能够通过后嫁接法修饰于SBA-15,修饰后仍保持十分有序的孔道结构。SBA-15通过改性后,其对毒死蜱的吸附量由100 mg·g^-1增加至195 mg·g^-1,且其对药物的缓释性能也得到改善。毒死蜱/铜席夫碱配合物改性SBA-15缓释体系显示出明显的pH值响应性,pH=3时的释药速率大于pH=11时,而在中性条件下的缓释效果相对最好。载药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。     

pH值响应性毒死蜱/铜席夫碱配合物改性SBA-15的制备及缓释性能

以3-氨丙基三乙氧基硅烷(APTES)、水杨醛和铜离子为改性剂,通过后嫁接法制得铜席夫碱配合物改性SBA-15(Cu-SBA-15),并以毒死蜱为模型药物,制备了毒死蜱/铜席夫碱配合物改性SBA-15缓释体系。利用TEM、SEM、XRD、N2吸附-脱附、TG、FTIR和XPS对SBA-15、氨基改性SBA-15(NH_2-SBA-15)、水杨醛希夫碱改性SBA-15(SA-SBA-15)的形貌、结构和Cu-SBA-15的配位情况进行了表征,考察了SBA-15在改性前后对毒死蜱的吸附量和缓释性能,并着重探究了毒死蜱/铜席夫碱配合物改性SBA-15载药体系在不同pH值下的释药行为。结果表明,APTES和水杨醛能够通过后嫁接法修饰于SBA-15,修饰后仍保持十分有序的孔道结构。SBA-15通过改性后,其对毒死蜱的吸附量由100 mg·g~(-1)增加至195 mg·g~(-1),且其对药物的缓释性能也得到改善。毒死蜱/铜席夫碱配合物改性SBA-15缓释体系显示出明显的pH值响应性,pH=3时的释药速率大于pH=11时,而在中性条件下的缓释效果相对最好。载药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。     

Controlled drug release from bifunctionalized mesoporous silica

Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups.     

基于HPMCP包覆介孔SBA-15的pH敏感药物缓释系统

以肠溶性包衣材料羟丙甲纤维素邻苯二甲酸酯(HPMCP)为原料,在负载法莫替丁(Famo)的SBA-15药片表面包覆聚合物膜,成功制备了一种新型的pH敏感药物缓释系统, 并考察了此缓释系统在不同pH释放环境中的释放行为. 结果表明: 在模拟胃液中(SGF, pH=1.2),HPMCP能致密包覆在药片表面,从而明显延缓Famo的释放速度;而在模拟肠液中(SIF, pH=7.5),HPMCP能够迅速溶于缓释溶液中,因而对Famo释放速度的影响甚微. 因此,可以将这种新型智能药物缓释系统应用于肠道靶向给药.     

Encapsulation hemoglobin in ordered mesoporous silicas: Influence factors for immobilization and bioelectrochemistry

The encapsulation of hemoglobin (Hb) on the mesoporous silicas SBA-15 and Au-doped SBA-15 (Au-SBA-15) has been studied as a model protein adsorption system. The influences of solution pH, structure of mesoporous silicas and gold nanoparticles incorporation on Hb immobilization are investigated in detail. The spectral characteristics of Hb/SBA-15 and Hb/Au-SBA-15 nanoconjugate show an absorption curve quite similar to that of native Hb, indicating that Hb retains its higher-order structure in the mesopores of SBA-15. Direct electrochemistry of Hb is obtained when Hb is adsorpted by mesoporous silicas SBA-15 or Au-SBA-15. Moreover, Hb/Au-SBA-15 exerts enhancing electron transfer ability because of the Au incorporation. Additionally, the Hb/Au-SBA-15 displays good electrocatalytic reduction of hydrogen peroxide with a detection limit of 1.0 μM, about 3 times as low as that for the Hb/SBA-15. The Hb/Au-SBA-15 exhibits higher peroxidase-like activity with the apparent Michaelis–Menton constant (K_m) of 2.87 mM, significantly lower than the 7.78 mM value for the Hb/SBA-15.     

Novel modified nanoporous silica for oral drug delivery: loading and release of clarithromycin

Nanoporous silica SBA-15 was prepared to evaluate its application as an oral drug delivery system. A series of surface-functionalized nanopore materials as efficient clarithromycin delivery carriers was investigated. An efficient pH-responsive carrier system was constructed by hydrogen bond interaction between carboxyl and hydroxyl groups in the clarithromycin and the amine group in modified SBA-15. HPLC analyses of clarithromycin were run on a C₁₈ column using a mobile phase comprised of potassium dihydrogen phosphate, acetonitrile and methanol (30:40:30, v/v/v). Active molecules such as clarithromycin could be stored and released from the pore voids of SBA-15 by changing the pH. The amount of clarithromycin stored in the pores of nanoporous silica based on TREN [tris(2-aminoethyl) amine]-modified SBA-15 rods was up to 46 ± 4.8 wt% at pH 8. In addition, when the pH was below 4, clarithromycin was steadily released from the pores of SBA-15 (up to 97 wt% in simulated gastric medium).     

Highly efficient enrichment and subsequent digestion of proteins in the mesoporous molecular sieve silicate SBA-15 for matrix-assisted laser desorption/ionization mass spectrometry with time-of-flight/time-of-flight analyzer peptide mapping

Based on a previous study of protein digestion inside the nanoreactor channels of the mesoporous molecular sieve silicate SBA-15 (Chem. Eur. J. 2005, 11: 5391), we have developed a highly efficient enrichment and subsequent tryptic digestion of proteins in SBA-15 for matrix-assisted laser desorption/ionization mass spectrometry with time-of-flight/time-of-flight analyzer (MALDI-TOF/TOF) peptide mapping. The performance of the method is exemplified with myoglobin and cytochrome c. First, protein adsorption isotherms for two standard proteins with a range of initial concentration of proteins were investigated at room temperature. The results revealed that the kinetic adsorption rate of a protein within SBA-15 was independent of initial protein concentration, and a 15-min protein enrichment within SBA-15 could be enough for protein identification in biological samples. It was noticed that no washing steps were needed to avoid protein loss due to desorption from the mesochannels into solution. Second, protein digestion inside the channels of SBA-15 was also optimized. After adsorption of proteins into SBA-15 in 15 min, the trypsin solution (pH 8) was directly added to the SBA-15 beads with immobilized proteins by centrifugation, and then the digestion was performed for 15 min at 37 degrees C. It was observed that a higher peptide sequence covering of 98% for myoglobin was obtained by MALDI-TOF/TOF analysis, compared to in-solution digestion. So the protein digestion inside SBA-15 was proved to be significantly faster and yielded a better sequence coverage. The new procedure allows for rapid protein enrichment and digestion inside SBA-15, and has great potential for protein analysis.     

pH值调控构建的纳米Ni-W催化剂用于纤维素氢解制多元醇的研究

采用等体积浸渍法制备了双金属Ni-W催化剂，并研究了制备过程中前驱体溶液pH值对活性的影响。柠檬酸和氢氧化钾分别作为酸碱调节剂将前驱体溶液pH值调节至0.83、1.00、3.09、5.00、7.03、8.97和11.0。纤维素氢解反应结果表明，当前驱体溶液的pH值为1.00时，在氢压为5.0 MPa、温度为518 K的反应条件下，得到低碳（C_2，3）多元醇的总收率为74.5%。此外，通过BET和SEM表征了催化剂的物理性质。其比表面积为330-450 m²/g，且在高温煅烧下SBA-15仍保持良好的水热稳定性。TEM和SEM-EDX结果显示，催化剂粒子在载体表面分散性较好，但也有少量的聚集现象。XRD表征表明，NiO等物种的还原程度明显受到pH值的影响，且镍、钨物种的相态也存在着显著不同。     

5-氟尿嘧啶在pH敏感型分子筛控释载体中的缓释行为

以肠溶性的羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)作为包覆材料,制备了HPMCP包覆的SBA-15介孔分子筛药物控释载体(HPMCP/SBA-15),并考察了抗癌药物5-氟尿嘧啶(5-Fu)负载于控释载体后,在不同pH释放环境中的释放行为.结果表明,在模拟胃液中(pH=1.2),HPMCP能明显地延缓5-Fu的释放速度;药物释放4h后,其释放率仅为15%.而在模拟肠液中(pH=7.5)HPMCP迅速溶解,对5-Fu释放速度的影响甚微;药物释放4h后,释放率可达到80%.与此同时,包覆膜的干燥温度影响5-Fu的释放行为,干燥温度越高,药物在模拟胃液中的释放速度越慢.     

Bifunctionalized SBA-15 as a novel micropipette tip sorbent for selective removal and enrichment of biomolecules

Selective enrichment or removal of specific proteins prior to analysis can minimize nonspecific interferences as well as information loss, which has been an important issue in current proteomics fields. In this work, two kinds of mesoporous silica SBA-15 (mean pore diameter of 5 nm and 7 nm), bifunctionalized with quaternary ammonium and C18 groups via silylanization reaction, was used to investigate the adsorption behavior for different proteins (bovine serum albumin (BSA), ovalbumin (OVA), hemoglobin (Hb), lysozyme (Lys) and cytochrome c (cyt c)). As possessing anion exchange (quaternary ammonium) groups, the bifunctionalized SBA-15 showed selective adsorption of the negative charged proteins, BSA and OVA. Based on these properties, sequential fractionation based on different SBA-15 materials as micropipette tip sorbents was developed for sample preparation prior to protein analysis. As expected, after the sequential treatment of the sample, the detection signal of the high abundant BSA was significantly decreased and that of the low abundant cyt c was obviously enlarged, which solved the problem that low abundant protein was suppressed by adjacent high abundant protein. The sample preparation technique significantly improved protein identification and this sequential fractionation approach could be potentially applied to extend information on the protein identification for biological samples with a wide dynamic range.     

Investigation of the mechanism of protein adsorption on ordered mesoporous silica using flow microcalorimetry

The adsorption of bovine serum albumin (BSA) and lysozyme (LYS) on siliceous SBA-15 with 24 nm pores was studied using flow microcalorimetry; this is the first attempt to understand the thermodynamics of protein adsorption on SBA-15 using flow microcalorimetry. The adsorption mechanism is a strong function of protein structure. Exothermic events were observed when protein–surface interactions were attractive. Entropy-driven endothermic events were also observed in some cases, resulting from lateral protein–protein interactions and conformational changes in the adsorbed protein. The magnitudes of the enthalpies of adsorption for primary protein–surface interactions decrease with increased surface coverage, indicating the possibility of increased repulsion between adsorbed protein molecules. Secondary exothermic events were observed for BSA adsorption, presumably due to secondary adsorption made possible by conformational changes in the soft BSA protein. These secondary adsorption events were not observed for lysozyme, which is structurally robust. The results of this study emphasize the influence of solution conditions and protein structure on conformational changes of the adsorbed protein and the value of calorimetry in understanding protein–surface interactions.     

可生物降解肝素钠/两性壳聚糖复合物用于蛋白药物pH响应释放研究

制备了一类可生物降解肝素钠两性壳聚糖复合物(HPACS),并探索将其用于蛋白药物pH响应释放.两性壳聚糖由壳聚糖与丙烯酸加成反应得到,丙烯酸取代度可通过丙烯酸壳聚糖投料比调控;用胶体与pH浊度滴定研究了肝素钠与两性壳聚糖的复合作用,发现两组分在一定pH范围内能通过静电相互作用形成复合物,复合转变临界pH(pHΦ)与两性壳聚糖中丙烯酸取代度有关,取代度越低,pHΦ值越高.以牛血清白蛋白(BSA)为模型,测定了其在复合物中包埋及不同pH介质中的释药行为.结果表明,BSA可以在非常温和条件下有效包埋于复合物中,包埋率接近100%;BSA从复合物中释放具有很高的pH响应性,释放转变在很窄的pH范围内(<0.4pH单位)完成,释放转变临界pH(pH′Φ)可由两性壳聚糖中丙烯酸取代度调控.复合物形成和蛋白质释放在对pH依赖性上存在很好的相关性.同时还发现,在中性介质中(pH7.4),复合物对BSA具有很好的缓释作用,BSA持续释放时间可达15天左右.     

Polysaccharide-modified iron oxide nanoparticles as an effective magnetic affinity adsorbent for bovine serum albumin

The magnetic separation technique based on magnetic iron oxide nanoparticles (MNPs) has potential applications in protein adsorption and purification, enzyme immobilization, cell sorting, nucleic acid detachment, and drug release. However, the naked MNPs are often insufficient for their hydrophilicity, colloidal stability, and further functionalization. To overcome these limitations, chitosan was firstly carboxymethylated and then covalently conjugated on the surface of the MNPs ranging in size from about 5 to 15 nm, which were prepared by co-precipitating iron (II) and iron (III) in alkaline solution and then treating under hydrothermal conditions. It was found that such modification did not result in the phase change of the MNPs, and the resultant modified nanoparticles were still superparamagnetic. In particular, the colloidal stability of MNPs in aqueous suspension was improved after the surface modification. By investigating the adsorption of bovine serum albumin (BSA) on the modified MNPs, it was observed that the adsorption capacity of the BSA on the modified MNPs increased rapidly within several minutes and then reached the maximum value at about 10 min. The adsorption equilibrium isotherm could be fitted well by the Langmuir model. The medium pH affected greatly the adsorption of the BSA. The maximum adsorption of the BSA occurred at the pH value close to the isoelectric point of the BSA, with a saturation adsorption amount of 94.45 mg/g (25 °C). For the BSA feed concentration of 1.017 mg/ml, a high desorption percentage of 91.5% could be achieved under an alkaline condition (pH 9.4).     

Ti-SBA-15介孔材料用于磷酸化肽的高效富集

结合基质辅助激光解吸飞行时间质谱(MALDI-TOF MS)检测技术,考察了Ti-SBA-15介孔材料对β-酪蛋白酶解产物中磷酸化肽的选择性富集性能。实验结果显示,含Ti和Si物质的量比为0.08的Ti-SBA-15介孔材料可选择性地对β-酪蛋白酶解产物中的磷酸化肽进行选择性富集;对于β-酪蛋白和牛血清白蛋白物质的量比为1:100的蛋白质酶解混合液,Ti-SBA-15仍能实现对其磷酸化肽的有效富集。上述结果表明,作为一种多孔、高比表面积的磷酸化多肽的选择性吸附材料,Ti-SBA-15有望在磷酸化蛋白质组的分析中得到广泛的应用。     

Chitosan‐Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery

A series of thermo/pH sensitive N‐succinyl hydroxybutyl chitosan (NSHBC) hydrogels with different substitution degrees of succinyl are prepared for drug delivery. Rheology analysis shows that the gelation temperature of NSHBC hydrogels is 3.8 °C higher than that of hydroxybutyl chitosan (HBC) hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors. After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0% at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high adaptability to soluble drugs and pH sensitivity triggered release, indicating that NSHBC hydrogels have promising applications in oral drug delivery.     

Synthesis, characterization and sustaining controlled release effect of mesoporous SBA-15/ramipril composite drug

A loading of ramipril in SBA-15 (Santa Barbara Amorphous) mesoporous material was studied. (SBA-15)-ramipril composite material was characterized by chemical analysis, infrared spectroscopy, powder X-ray diffraction, low temperature N₂ adsorption–desorption at 77 K characterization techniques. Ramipril drug release processes from SBA-15 host to simulated body fluid (SBF), simulated gastric juice (SGJ), simulated intestinal fluid (SIF) were monitored in a simulated way and actions of the sustained release of (SBA-15)-ramipril was studied. The results showed that the loading amount of ramipril drug in SBA-15 was 90.30 mg/g. The cumulative sustained release rate of ramipril composite drug in SBF achieved 99.7 % after 27 h. When the sustained release of composite drug in SGJ was 8 h, the maximum cumulative sustained release ratio achieved 54.9 %. When the sustained release of composite drug was 9 h in SIF, the maximum cumulative sustained release ratio achieved 34.9 %. The method described in this study is suitable for carrying ramipril drug on SBA-15, and a new carrier to load ramipril drug was found. Meanwhile, the efficacy of ramipril drug and time efficacy could be improved.     

Effect of mesopores on solidification of sirolimus self-microemulsifying drug delivery system

The mesoporous silica materials had a high loading efficiency of sirolimus-SMEDDS. The length of the mesopores played a more important role than the pore diameter in drug dissolution and in vivo absorption.     

Synthesis and characterization of mesoporous SBA-15/propranolol hydrochloride for controlled drug release study

Propranolol hydrochloride was incorporated into SBA-15 mesoporous material host by impregnation method to obtain host-guest nanocomposite material (SBA-15)-propranolol hydrochloride. By spectrophotometry, the amount of propranolol hydrochloride assembly was determined to be 382.05?mg/g (drug/SBA-15). Powder X-ray diffraction test results indicated that during the process of incorporation the framework of the molecular sieve was not destroyed and the molecular sieve still remained its structure ordering. Fourier transform infrared spectra showed that the framework of the prepared host-guest material was remained in good condition. Low-temperature nitrogen adsorption-desorption at 77?K results showed that the surface area and the pore volume of (SBA-15)-propranolol hydrochloride host-guest material decreased compared to those of the host molecular sieve, indicating that propranolol hydrochloride guest molecules have partially occupied the channels of the molecular sieve. Transmission electron microscopy and scanning electron microscopy results indicated that two-dimensional hexagonal mesoporous pore channels of the molecular sieve were retained and (SBA-15)-propranolol hydrochloride composite material remained fibrous crystals and the average diameter of sample was 336?nm. It was discovered in drug release principle in the simulated body fluid that the effective release time of the drug reached 30?h and the maximum cumulative released amount of propranolol hydrochloride was 99.3?%. When drug release time arrived at 5?h in the simulated gastric juice, the maximum cumulative released amount was 51.2?%.When drug release time arrived at 9?h in the simulated intestinal fluid, the maximum cumulative released amount was 70.1?%. The drug sustained release results showed that SBA-15 is a well-controlled drug release carrier.     

Physical and chemical adsorption of Mucor javanicus lipase on SBA-15 mesoporous silica. Synthesis, structural characterization, and activity performance

In this work a sample of SBA-15 mesoporous silica was synthesized and characterized by TEM, XRD, and N2 adsorption. The sample had a high value of specific surface area (1007 m2 g(-1)) and total pore volume (2.1 cm3 g(-1)). The pore diameter was 67 angstroms, so it was large enough to accommodate protein molecules inside the channels. Immobilization by physical adsorption of a commercial lipase preparation from Mucor javanicus was performed at different pH values (pH 5-8). pH 6 gave the highest lipase loading and hydrolytic activity of the corresponding biocatalyst. Chemical modification of the SBA-15 via glutardialdehyde allowed also the enzyme immobilization through chemical adsorption. This preparation was active toward tributyrin hydrolysis. On the contrary, very low activity toward triolein hydrolysis was observed. The reduction of the size of the channels due the immobilization process has been suggested as a possible explanation.