Functionalized mesoporous silica materials for controlled drug delivery

In the past decade, non-invasive and biocompatible mesoporous silica materials as efficient drug delivery systems have attracted special attention. Great progress in structure control and functionalization (magnetism and luminescence) design has been achieved for biotechnological and biomedical applications. This review highlights the most recent research progress on silica-based controlled drug delivery systems, including: (i) pure mesoporous silica sustained-release systems, (ii) magnetism and/or luminescence functionalized mesoporous silica systems which integrate targeting and tracking abilities of drug molecules, and (iii) stimuli-responsive controlled release systems which are able to respond to environmental changes, such as pH, redox potential, temperature, photoirradiation, and biomolecules. Although encouraging and potential developments have been achieved, design and mass production of novel multifunctional carriers, some practical biological application, such as biodistribution, the acute and chronic toxicities, long-term stability, circulation properties and targeting efficacy in vivo are still challenging.     

Bioresponsive mesoporous silica nanoparticles for triggered drug release

Mesoporous silica nanoparticles (MSNPs) have garnered a great deal of attention as potential carriers for therapeutic payloads. However, achieving triggered drug release from MSNPs in vivo has been challenging. Here, we describe the synthesis of stimulus-responsive polymer-coated MSNPs and the loading of therapeutics into both the core and shell domains. We characterize MSNP drug-eluting properties in vitro and demonstrate that the polymer-coated MSNPs release doxorubicin in response to proteases present at a tumor site in vivo, resulting in cellular apoptosis. These results demonstrate the utility of polymer-coated nanoparticles in specifically delivering an antitumor payload.     

Synthesis of pH-responsive mesoporous silica nanotubes for controlled release

A novel mesoporous silica tubes (MMT) which possessed pH-sensitive controlled release ability had been fabricated and synthesized by using carbon nanotubes (CNTs) as template. The sample replicated the morphologies of the CNTs successfully. The Brunauer–Emmett–Teller surface area of the materials can reach 1,017 m² g^?1 with the pore size of 3.8 nm. As a model drug, metformin HCl was applied to study the drug loading and control release ability of the materials. MMT possesses higher drug loading ratio (36 %) than that of MCM-41 (27.5 %). The release kinetics were studied in simulated gastric fluid (pH = 1.2) and in simulated proximal intestine fluid (pH = 7. 4), respectively. The result shows that the delivery systems exhibit well pH-sensitive control release ability and the as-synthesized materials have potential application in biomedical field.     

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.     

Magnetic-sensitive silica nanospheres for controlled drug release

Recently, magnetic silica-based nanospheres have received great attention and displayed magnificent potential for bioimaging and therapeutic purposes. This study provided a way to accelerate drug release from magnetic-sensitive silica nanospheres by controlled bursting to a therapeutically effective concentration by a high-frequency magnetic field (HFMF). The magnetic-sensitive silica nanospheres were synthesized by an in situ process, with particle sizes about 50 nm and able to release specific amounts of drug in a burst manner via short exposure to a HFMF. The HFMF accelerates the rotation of magnetic nanoparticles deposited in the silica matrix with generated heat energy and subsequently enlarges the nanostructure of the silica matrix to produce porous channels that cause the drug to be released easily. By taking these magnetic-responsive controllable drug release behaviors, the magnetic silica nanospheres can be designed for controlled burst release of therapeutic agents for especially urgent physiological needs.     

A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials

A series of mesoporous silica materials with similar pore sizes, different morphologies and variable pore geometries were prepared systematically. In order to control drug release, ibuprofen was employed as a model drug and the influence of morphology and pore geometry of mesoporous silica on drug release profiles was extensively studied. The mesoporous silica and drug-loaded samples were characterized by X-ray diffraction, Fourier transform IR spectroscopy, N₂ adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. It was found that the drug-loading amount was directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drug release profiles could be controlled by tailoring the morphologies of mesoporous silica carriers.     

pH-Triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids

Acid-decomposable, luminescent ZnO quantum dots (QDs) have been employed to seal the nanopores of mesoporous silica nanoparticles (MSNs) in order to inhibit premature drug (doxorubicin) release. After internalization into HeLa cells, the ZnO QD lids are rapidly dissolved in the acidic intracellular compartments, and as a result, the loaded drug is released into the cytosol from the MSNs. The ZnO QDs behave as a dual-purpose entity that not only acts as a lid but also has a synergistic antitumor effect on cancer cells. We anticipate that these nanoparticles may prove to be a significant step toward the development of a pH-sensitive drug delivery system that minimizes drug toxicity.     

Dual pH and glucose sensitive gel gated mesoporous silica nanoparticles for drug delivery

A low-molecular-weight gel with dual pH and glucose sensitivity was designed as the gate controller for mesoporous silica nanoparticles (MSNs) to fabricate a smart drug delivery system. The smart gel caped MSNs could control the antidiabetic drug release via the detection of glucose and pH levels.     

pH-Controllable drug release using hydrogel encapsulated mesoporous silica

Amine-functionalized mesoporous SBA-15 silica loaded with bovine serum albumin (BSA) has been successfully encapsulated with a thin layer coating of poly(acrylic acid) PAA, with the entrapped BSA being released from the PAA-encapsulated SBA-15 at the higher pH value of 7.4 rather than at the lower pH value of 1.2. This novel drug delivery system has a potential application in the release of protein drug to the site of higher pH value, such as small intestine or colon.     

Temperature-sensitive polypeptide brushes-coated mesoporous silica nanoparticles for dual-responsive drug release

A multifunctional nanohybrid based on mesoporous silica nanoparticle and biocompatible polypeptide was fabricated for targeted and dual-responsive therapy of tumor cells.     

Temperature-sensitive polypeptide brushes-coated mesoporous silica nanoparticles for dual-responsive drug release

A biopolymer-inorganic hybrid system (MSN@PBLGF) is designed and fabricated from mesoporous silica nanoparticles (MSNs) and folic acid (FA)-terminated temperature-sensitive synthetic polypeptide, i.e., poly(γ-benzyl-l-glutamate) (PBLG) derivative, through a thiol-disulfide exchange reaction, where MSNs with high drug loading capacity serve as drug nanocarriers and the biocompatible PBLG biopolymer brushes installed on MSN surface through disulfide bonds endow the system with tumor-specific recognition ability and GSH/temperature dual-stimuli responsiveness. Controlled drug release experiments indicate that DOX can be tightly hosted in the system with limited premature release, but efficiently released in response to an increased concentration of GSH and/or an elevated temperature. Intracellular experiments demonstrate that the DOX-loaded MSN@PBLGF nanohybrid shows outstanding cellular uptake and cell-growth inhibition effects on human lung cancer cell line A549 in comparison with healthy human cells such as hepatocyte cells LO2.     

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.     

Enhanced release of itraconazole from ordered mesoporous SBA-15 silica materials

This in vitro study reports on the enhanced release of the hydrophobic drug itraconazole from the ordered mesoporous SBA-15 silica material and on the existence of a critical mesopore diameter for enhancing release.     

A glucose-responsive controlled release system using glucose oxidase-gated mesoporous silica nanocontainers

A glucose-responsive controlled-release system based on the competitive combination between glucose oxidase, glucosamine and glucose has been described, which exhibits perfect controlled release properties and high selectivity for glucose over other monosaccharides. This paved the way for a new generation of stimuli-responsive delivery systems.     

Functionalized mesoporous silica nanoparticle-based visible light responsive controlled release delivery system

A supramolecular assembly for visible light responsive release of cargo molecules is presented. Sulforhodamine 101 was loaded inside the mesopores of mercaptopropyl-functionalized mesoporous silica nanoparticles (MP-MSN) and entrapped by mercaptopropyl-coordinated Ru(bpy)(2)(PPh(3))-moieties. Irradiation with visible light triggers the release of capping species and loaded molecules.     

Poly(lactic acid)-coated mesoporous silica nanosphere for controlled release of venlafaxine

Two types of mesoporous silica nanospheres (MSNs) were synthesized for use as controlled-release agents. One was prepared by grafting with 5,6-dihydroxyhexylsilane (DH-MSN) and the other one by further coating with cholic acid-crosslinked poly(lactic acid) (CA-PLA-MSN). We studied the release of the antidepressant venlafaxine from each of the materials in simulated gastric fluid (SGF), in simulated gastric acid solution (SGA), and in simulated intestinal fluid without pancreatin (SIF). The CA-PLA-MSN material was able to significantly delay the release of the drug in intestinal condition compared with gastric acid surrounding due to the fast decomposition rate of PLA in gastric acid. Moreover, it successfully avoided the initial burst to a certain extent in SGF. The enzyme pepsin played a favorable obstruct role in both DH-MSN and CA-PLA-MSN systems to reduce release rate. A model based on Weibull model was built to fit the release results, and based on it, the mechanisms about release processes were brought out tentatively.     

Enhanced release of the poorly soluble drug itraconazole loaded in ordered mesoporous silica

It is known that the energy of the amorphous state of itraconazole loaded in ordered mesoporous materials is high relative to that of the crystalline state and is responsible for enhanced solubility and dissolution rate. We investigated the effects of particle size(0.7–5μm), mesostructure(2D p6 mm, cubic Ia-3d and cubic Fm-3m) and pore size(2.2–15.4 nm) of mesoporous silicas on the release performance of itraconazole. Results indicated that the release performance was not influenced by the particle sizes tested here, that the release performance increased with increasing pore diameter due to the lower probability of drug molecules colliding to recrystallize in large pores, and that the release performance was decreased in the cage-type pore structure(Fm-3m) compared to that in the cylindrical pore structures(p6mm and Ia-3d) because of the small entrance to the cagelike pores that retards the drug release.     

Bioresponsive controlled release using mesoporous silica nanoparticles capped with aptamer-based molecular gate

This communication describes the design of a novel and general bioresponsive controlled-release mesoporous silica (MS) nanoparticles system based on aptamer-target interactions. In this system, the pores of MS were capped with Au nanoparticles modified with aptamer (ATP aptamer in this case). By a competitive displacement reaction, the Au nanoparticles were uncapped in the presence of ATP molecule, and the cargo was released. Our results demonstrated that the aptamer-target interaction may be a promising route for the design of custom-made controlled-release nanodevices specifically governed by target biomolecules. Since aptamers have been obtained for a broad range of targets, including several cancer biomarkers, we believe that this aptamer-based controlled-release system should have an equally broad spectrum of applications.