Silica Materials for Medical Applications

The two main applications of silica-based materials in medicine and biotechnology, i.e. for bone-repairing devices and for drug delivery systems, are presented and discussed. The influence of the structure and chemical composition in the final characteristics and properties of every silica-based material is also shown as a function of the both applications presented. The adequate combination of the synthesis techniques, template systems and additives leads to the development of materials that merge the bioactive behavior with the drug carrier ability. These systems could be excellent candidates as materials for the development of devices for tissue engineering

Fabrication and characterization of Ag- and Ga-doped mesoporous glass-coated scaffolds based on natural marine sponges with improved mechanical properties

Natural marine sponges were used as sacrificial template for the fabrication of bioactive glassbased scaffolds. After sintering at 1050 ºC, the resulting samples were additionally coated with a sol silicate solution containing biologically active ions (Ag and Ga), well-known for their antibacterial properties in comparison with standard scaffolds made by PU foam templates. The produced scaffolds were characterized by superior mechanical properties (maximum compressive strength of 4 MPa) and total porosity of ~80%. Direct cell culture tests performed on the uncoated and coated samples showed positive results in terms of adhesion, proliferation, and differentiation of MC3T3-E1 cells. Moreover, vascular endothelial growth factor (VEGF) secretion from cells in contact with scaffold dissolution products was measured after 7 and 10 days of incubation, showing promising angiogenic results for bone tissue engineering applications. The antibacterial potential of the produced samples was assessed by performing agar diffusion tests against both Gram-positive and Gram-negative bacteria.EU Horizon 2020 project COACH 64255

High resolution transmission electron microscopy: A key tool to understand drug release from mesoporous matrices

This work demonstrates that high resolution transmission electron microscopy (HRTEM) is an essential tool to understand drug delivery performance of mesoporous silica materials, mainly those submitted to functionalization processes involving harsh conditions that may affect the mesostructure. Herein an SBA-15-type mesoporous material bearing Si(CH2)(2)P(O)(OCH2CH3)(2) groups was synthesized following the co-condensation route. Then, the resulting material was treated with 37 wt% HCl to convert ethylphosphonate groups to ethylphosphonic acid groups. The proper dealkylation of ethoxy groups following acid treatment was confirmed by FTIR and CP-MAS H-1 -> C-13 solid state NMR, which indicated the presence of Si(CH2)(2)P(O)(OH)(2) functionalities in the treated sample. Characterization of mesoporous materials by XRD diffraction and N-2 adsorption points to well-ordered SBA-15 structures in both untreated and acid-treated samples. Nonetheless, a deep study by HRTEM reveals that the acid-treatment provokes noticeable loss of mesostructural order, only remaining small crystalline domains. This structural damage does not influence cargo loading but it severely affects the release of molecules confined into the mesopores, as concluded from in vitro delivery tests using cephalexin as model drug. Thus, whereas untreated sample showed a sustained diffusion-controlled drug release during more than 2 weeks, 100% of the loaded drug was released only after 10 h from treated sample. This abrupt burst effect cannot be explained on the basis of the existing matrix-drug interactions, whose nature and extension is quite similar under the release conditions for both samples. Thus, it can be only understood on the basis of the mesostructural damage revealed by HRTEM studies. (C) 2016 Elsevier Inc. All rights reserved

Drug Release from Ordered Mesoporous Silicas

The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for each drug, are comprehensively listed. Next, the factors influencing the release of drugs from SMMs and the strategies used to control the drug delivery, specially the chemical functionalization of the silica surface, are discussed. In addition, how all these factors were gathered in a kinetic equation that describes the drug release from the mesoporous matrixes is explained. The new application of molecular modeling and docking in the investigation of the drug delivery mechanisms from SMMs is also presented. Finally, the new approaches under investigation in this field are mentioned including the design of smart stimuli-responsive materials and other recent proposals for a future investigation

Electron microscopy for inorganic-type drug delivery nanocarriers for antitumoral applications: What is possible to see?

The use of nanoparticles able to transport drugs, in a selective and controlable manner, directly to diseased tissues and cells have improved the therapeutic arsenal for addressing unmet clinical situations. In the recent years, a vast number of nanocarriers with inorganic, organic, hybrid and even biological nature have been developed, expecially for their application in oncology fied. The exponential growing in the nanomedicine field would not have been possible without the also rapid expansion of electron microscopy techniques, which allow a more precise observation of nanometric objects. The use of these techniques provides a better understanding of the key parameters which rule their synthesis and behavior. In this review, the recent advances performed in the application of inorganic nanoparticles for clinical uses and the role which has played electron microscopy will be presented

Decidua-derived mesenchymal stem cells as carriers of mesoporous silica nanoparticles. In vitro and in vivo evaluation on mammary tumors

The potential use of human Decidua-derived mesenchymal stem cells (DMSCs) as a platform to carry mesoporous silica nanoparticles in cancer therapy has been investigated. Two types of nanoparticles were evaluated. The nanoparticles showed negligible toxicity to the cells, a fast uptake and a long retention inside them. Nanoparticle location in the cell was studied by colocalization with the lysosomes. Moreover, the in vitro and in vivo migration of DMSCs towards tumors was not modified by the evaluated nanoparticles. Finally, DMSCs transporting doxorubicin-loaded nanoparticles were capable of inducing cancer cell death in vitro

Mesoporous silica nanoparticles as a new carrier methodology in the controlled release of the active components in a polypill

Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12.5/2.5/25/40 weight ratio. The procedure is based onmesoporous silica nanoparticles (MSN) with MCM-41 structure (MSN-41) used as carrier, aimed to control release of the four drugs included in the polypill. In vitro release data were obtained by HPLC and the curves adjusted with a kinetic model. To explain the release results, a molecular model was built to determine the drug-matrix interactions, and quantum mechanical calculations were performed to obtain the electrostatic properties of each drug. Amlodipine, losartan and simvastatin were released from the polypill-MSN-41 system in a controlled way. This would be a favourable behavior when used clinically because avoid too quick pressure decrease. However, the diuretic hydrochlorothiazide was quickly released from our system in the first minutes, as is needed in hypertensive urgencies. In addition, an increase in the stability of amlodipine and hydrochlorothiazide occurred in the polypill-MSN-41 system. Therefore, the new way of polypill dosage proposed can result in a safer and effective treatment. (C) 2016 Elsevier B.V. All rights reserved