Mesoporous materials for drug delivery

Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.     

Biomimetic strengthening polylactide scaffold materials for bone tissue engineering

In this paper, a new polylactide (PLA)-based scaffold composite by biomimetic synthesis was designed. The novel composite mainly consists of nano-hydroxyapatite (n-HA), which is the main inorganic content in natural bone tissue for the PLA. The crystal degree of the n-HA in the composite is low and the crystal size is very small, which is similar to that of natural bone. The compressive strength of the composite is higher than that of the PLA scaffold. Using the osteoblast culture technique, we detected cell behaviors on the biomaterial in vitro by SEM, and the cell affinity of the composite was found to be higher than that of the PLA scaffold. The biomimetic three-dimensional porous composite can serve as a kind of excellent scaffold material for bone tissue engineering because of its microstructure and properties. Translated from Journal of Hunan University (Natural Sciences), 2006, 33(2) (in Chinese)     

Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials’ relative adsorption and release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of ∼2.7-3.3 nm and moderate to high surface areas up to ∼1000 m²/g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model.     

Comparison of micro- and mesoporous inorganic materials in the uptake and release of the drug model fluorescein and its analogues

The uptake of the three species of the drug model fluorescein (fluorescein sodium salt (FNa), fluorescein free acid (F), and fluorescein diacetate (FDA)) by zeolite NaX and the mesoporous zeotype MCM-41 was investigated as well as their release rates into solutions at pH 7 and pH 4.5. UV/Vis analysis was carried out at a wavelength of 490 nm. Uptakes of the sodium salt of 9 % for zeolite X and 14 % for MCM suggest little penetration of the pores. The use of ethanol as the loading solvent for F resulted in little uptake for both zeolitic materials due to the successful competition of the ethanol for binding sites. Use of acetone (weaker proton acceptor) as loading solvent significantly improved the uptake of F to 17 % and 12 % for zeolite X and MCM, respectively, whilst the uptake of FDA in acetone increased still further to 22 % and 17 % for zeolite X and MCM, respectively. Generally there was a large initial release of the fluorescein analogues from the surface of the zeolites with very little further increase over time. The prescence of an esterase enzyme in the release medium of FDA tripled the release from MCM to 15 % but left the release from zeolite X unaffected at 6 %. The results obtained show that uptake of fluorescein and its analogues is dependent on the loading solvent used, the amount released is influenced by not only the solvent but the pH and the presence of enzymes in the release medium.     

有序介孔材料在生物医药领域中的应用

本文简述了有序介孔材料的特性,详细介绍了其在生物医药领域中的应用研究,如用于酶的固定化、生物传感器、药物的包埋和控释、生物活性材料、生物分子的吸附和分离等,阐述了不同类型的有序介孔材料在这些应用中的性能以及为适用于该领域应用进行的材料开发和结构修饰,最后对材料的改进和应用前景进行了展望。     

Sodium alginate/magnesium oxide nanocomposite scaffolds for bone tissue engineering

A simple 2‐step method, consisting of film casting and polyvinyl alcohol leaching, is proposed to prepare magnesium oxide (MO) nanoparticle‐reinforced sodium alginate scaffolds with right properties for bone tissue engineering. The cytocompatibility of the as‐prepared scaffolds was also evaluated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium‐bromide yellow tetrazole assay test, wherein chondrocyte cells had been considered as target cells. According to the results, the ensuing sodium alginate nanocomposites, containing 4‐wt% MO nanoparticles, demonstrated the highest physical and mechanical properties after leaching step. The Young modulus of sodium alginate/4‐wt% MO was improved about 44%, in comparison with that of the pure alginate sample. Furthermore, incorporating MO nanoparticles up to 4 wt% controlled the liquid uptake capacity of scaffolds vis‐à‐vis the resultant pure sodium alginate sample. Moreover, with increasing the nanoparticle content, the antibacterial properties of scaffolds enhanced, but their degradation rates under in vitro conditions tapered off. With the introduction of 3‐ and 4‐wt% MO, the average diameter of the bacterial zone of the scaffold samples reduced to less than 10 mm², suggesting an insensitive antimicrobial performance, compared with the pure sodium alginate and the samples with 1‐ and 2‐wt% MO content, which exhibit antimicrobial sensitivity. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium‐bromide assay test also revealed the cultivated chondrocyte cells on the 4‐wt% MO nanoparticle‐reinforced scaffold possessed better interaction as well as appropriate cell attachment and proliferation than the pristine sodium alginate sample.     

NIR-triggered drug delivery system based on phospholipid coated ordered mesoporous carbon for synergistic chemo-photothermal therapy of cancer cells

Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy. However, traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties, as it results in complicated synthesis process, inefficient photothermal effects and hindered NIR-mediated drug release. Herein we report a facile synthesis of a polyethylene glycol (PEG) linked liposome (PEG-liposomes) coated doxorubicin (DOX)-loaded ordered mesoporous carbon (OMC) nanocomponents (PEG-LIP@OMC/DOX) by simply sonicating DOX and OMC in PEG-liposomes suspensions. The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size (600 ± 15 nm), a negative surface potential (−36.70 mV), high drug loading (131.590 mg/g OMC), and excellent photothermal properties. The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells (MCF-7) and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity, confirming the PEG-LIP@OMC itself has excellent biocompatibility. The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release. Furthermore, cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemotherapy can provide higher therapeutic efficacy than respective monotherapies. With these excellent features, we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.     

Control of Drug Release through the In Situ Assembly of Stimuli‐Responsive Ordered Mesoporous Silica with Magnetic Particles

A site‐selective controlled delivery system for controlled drug release is fabricated through the in situ assembly of stimuli‐responsive ordered SBA‐15 and magnetic particles. This approach is based on the formation of ordered mesoporous silica with magnetic particles formed from Fe(CO)₅ via the surfactant‐template sol‐gel method and control of transport through polymerization of N‐isopropyl acrylamide inside the pores. Hydrophobic Fe(CO)₅ acts as a swelling agent as well as being the source of the magnetic particles. The obtained system demonstrates a high pore diameter (7.1 nm) and pore volume (0.41 cm³ g^?1), which improves drug storage for relatively large molecules. Controlled drug release through the porous network is demonstrated by measuring the uptake and release of ibuprofen (IBU). The delivery system displays a high IBU storage capacity of 71.5 wt %, which is almost twice as large as the highest value based on SBA‐15 ever reported. In vitro testing of IBU loading and release exhibits a pronounced transition at around 32 °C, indicating a typical thermosensitive controlled release.     

NIR-triggered drug delivery system based on phospholipid coated ordered mesoporous carbon for synergistic chemo-photothermal therapy of cancer cells

Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy. However, traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties, as it results in complicated synthesis process, inefficient photothermal effects and hindered NIR-mediated drug release. Herein we report a facile synthesis of a polyethylene glycol (PEG) linked liposome (PEG-liposomes) coated doxorubicin (DOX)-loaded ordered mesoporous carbon (OMC) nanocomponents (PEG-LIP@OMC/DOX) by simply sonicating DOX and OMC in PEG-liposomes suspensions. The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size (600±15 nm), a negative surface potential (-36.70 mV), high drug loading (131.590 mg/g OMC), and excellent photothermal properties. The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells (MCF-7) and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity, confirming the PEG-LIP@OMC itself has excellent biocompatibility. The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release. Furthermore, cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemotherapy can provide higher therapeutic efficacy than respective monotherapies. With these excellent features, we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.     

Periodic mesoporous organosilicas with co-existence of diurea and sulfanilamide as an effective drug delivery carrier

In this article we report the synthesis of new periodic mesoporous organosilicas (PMOs) with the co-existence of diurea and sulfanilamide-bridged organosilica that are potentially useful for controlled drug release system. The materials possess hexagonal pores with a high degree of uniformity and show long-range order as confirmed by the measurements of small-angle X-ray scattering (SAXS), N₂ adsorption isotherms, and transmission electron microscopy(TEM). FT-IR and solid state ²⁹Si MAS and ¹³C CP MAS NMR spectroscopic analyses proved that the bridging groups in the framework are not cleaved and covalently attached in the walls of the PMOs. It was found that the organic functionality could be introduced in a maximum of 10 mol% with respect to the total silicon content and be thermally stable up to 230 °C. The synthesized materials were shown to be particularly suitable for adsorption and desorption of hydrophilic/hydrophobic drugs from a phosphate buffer solution at pH 7.4.     

普鲁兰多糖在药物释放系统中的应用

本综述重点介绍了近年来普鲁兰多糖作为药物释放系统载体材料的研究进展及其在药物释放系统中的应用情况。     

A study of carboxylic-modified mesoporous silica in controlled delivery for drug famotidine

A series of pure silica MSU and carboxylic-modified MSU materials were prepared. The formation of mesoporous silica materials with terminal carboxylic groups on pore surface was performed by the acid-catalyzed hydrolysis of cyano to carboxylic. Then their potential applications in controlled drug delivery carriers were investigated. Drug famotidine was selected as a model molecule out of the consideration of the terminal amino groups in its molecule. The adsorption experiments show significant adsorption of famotidine on the carboxylic-modified MSU materials. And, the functionalization level of carboxylic groups has been found to be the key factor affecting the adsorption capacities of the modified MSU materials for famotidine. Subsequently, three kinds of release fluids, including simulated gastric medium, simulated intestinal medium, and simulated body fluid, were used to test the famotidine release rate from the carboxylic-modified MSU material. Obvious delayed effect has been observed for the famotidine release from the carboxylic-modified mesoporous silica material under the in vitro assays.     

Two sides to supramolecular drug delivery systems

Although still in its infancy, there is a rapidly increasing interest in the development of supramolecular drug delivery systems (SDDSs). As chemists, the most challenging task ahead of us is to narrow the gap between SDDSs development in the lab, and clinical drug carriers. Only then will we achieve our ultimate goal of the successful translation of SDDSs to life saving medicines.     

Release from silica SBA-3-like mesoporous fibers: cross-wall transport and external diffusion barrier.

The transport of guest molecules between adjacent pore channels (cross-wall transport) is the limiting factor in the release of guest molecules from SBA-3-like fibers. This specific mode of diffusion is identified by microscopic observation and studied quantitatively in a UV/Vis-monitored release experiment. Analysis of release curves reveals that the external particle surface offers resistance to the guest molecules passing through it (external diffusion barrier). This barrier is native to as-synthesized fibers and can be effectively modified to slow down the release. Extremely effective slowdown is achieved by deposition of a nanometer-thick layer of sodium silicate, that is, the guest molecules are then safely stored in the particles.