Nanoantibiotics Based in Mesoporous Silica Nanoparticles: New Formulations for Bacterial Infection Treatment.

This review focuses on the design of mesoporous silica nanoparticles for infection treatment. Written within a general context of contributions in the field, this manuscript highlights the major scientific achievements accomplished by professor Vallet-Regí's research group in the field of silica-based mesoporous materials for drug delivery. The aim is to bring out her pivotal role on the envisage of a new era of nanoantibiotics by using a deep knowledge on mesoporous materials as drug delivery systems and by applying cutting-edge technologies to design and engineer advanced nanoweapons to fight infection. This review has been divided in two main sections: the first part overviews the influence of the textural and chemical properties of silica-based mesoporous materials on the loading and release of antibiotic molecules, depending on the host-guest interactions. Furthermore, this section also remarks on the potential of molecular modelling in the design and comprehension of the performance of these release systems. The second part describes the more recent advances in the use of mesoporous silica nanoparticles as versatile nanoplatforms for the development of novel targeted and stimuli-responsive antimicrobial nanoformulations for future application in personalized infection therapies.

Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine- and Phosphorus-Doped Nanostructured Ti-6Al-4V Alloy Loaded With Gentamicin and Vancomycin.

Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine- and phosphorus-doped, bottle-shaped, nanostructured (bNT) Ti-6Al-4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti-6Al-4V loading with a mixture of GV, measuring the release of these antibiotics using high-performance liquid chromatography. Further, we describe bNT Ti-6Al-4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti-6Al-4V following a Boltzmann non-linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti-6Al-4V GV compared with control. In vivo study results show that bNT Ti-6Al-4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti-6Al-4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588-597, 2020.

Developments with multi-target drugs for Alzheimer's disease: an overview of the current discovery approaches.

Introduction: Alzheimer's disease (AD), the most common type of dementia among older adults, is a chronic neurodegenerative pathology that causes a progressive loss of cognitive functioning with a decline of rational skills. It is well known that AD is multifactorial, so there are many different pharmacological targets that can be pursued. Areas covered: The authors highlight the strategic value of privileged scaffolds in a multi-target lead compound generation against AD, exploring the concept of multi-target design, with a special emphasis on hybrid compounds. Hence, the most promising building blocks for designing and synthesizing hybrid anti-AD drugs are shown, while also presenting the more advanced hybrid compounds. Expert opinion: The available therapeutic arsenal for AD, designed under the traditional paradigm of 'one-drug/one target/one-disease', is based on the inhibition of brain acetylcholinesterase (AChE) to increase acetylcholine (ACh) levels. However, this classical approach has not been sufficiently effective when used to treat any multifactor-depending pathology (cancer, diabetes or AD). The multi-target drug concept has been quickly adopted by medicinal chemists. The basic research developments reported in recent years are a solid foundation that will pave the way for the construction of future AD therapeutics.

Antibiotic release from F-doped nanotubular oxide layer on TI6AL4V alloy to decrease bacterial viability.

We aimed to evaluate the release of two antibiotics: gentamicin and vancomycin loaded into F-doped nanotubular anodic oxide layers, as well as their bactericide effect. F-doped nanotubular oxide layers fabricated on Ti-6Al-4V loaded with gentamicin (Gm), vancomycin (Vm) and their mixture (Gm + Vm) by a previously described loading method. Antibiotic release was studied by RP-HPLC and by a biological method. Bactericidal activity was evaluated by a bacterial adherence protocol described previously using on three clinically important bacterial species. The antibiotic release steady up to 120 and 180 min for Gm and Vm, respectively, and despite the antibiotic concentration decreased, their biological activity was maintained over time. The number of living bacteria of three species tested on NT-Gm specimens was significantly lower than on NT specimens without antibiotics (P < 0.01). There are significant differences among NT-Gm and NT-Gm + Vm specimens (P < 0.05) for S. aureus 15981, S. epidermidis ATCC 35984, and P. aeruginosa ATCC 27853 and no differences between NT-Vm and NT-Gm + Vm for staphylococci (P > 0.05). In conclusion, this Gm + Vm loading method added to the properties of F-doped nanotubular oxide layers fabricated on Ti-6Al-4V, and therefore surfaces with antibacterial, biocompatible, tissue integration stimulating and spread-spectrum bactericidal properties can be obtained.

Bactericidal activity of the Ti-13Nb-13Zr alloy against different species of bacteria related with implant infection.

The Ti-6Al-4V alloy is one of the most commonly used in orthopedic surgery. Despite its advantages, there is an increasing need to use new titanium alloys with no toxic elements and improved biomechanical properties, such as Ti-13Nb-13Zr. Prosthetic joint infections (PJI) are mainly caused by Gram-positive bacteria; however, Gram-negative bacteria are a growing problem due to associated multidrug resistance. In this study, the bacterial adherence and viability on the Ti-13Nb-13Zr alloy have been compared to that of the Ti-6Al-4V alloy using 16 collection and clinical strains of bacterial species related to PJI: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa. When compared with the Ti-6Al-4V alloy, bacterial adherence on the Ti-13Nb-13Zr alloy was significantly higher in most staphylococcal and P. aeruginosa strains and lower for E. coli strains. The proportion of live bacteria was significantly lower for both Gram-negative species on the Ti-13Nb-13Zr alloy than on the Ti-6Al-4V alloy pointing to some bactericidal effect of the Ti-13Nb-13Zr alloy. This bactericidal effect appears to be a consequence of the formation of hydroxyl radicals, since this effect is neutralized when dimethylsulfoxide was added to both the saline solution and water used to wash the stain. The antibacterial effect of the Ti-13Nb-13Zr alloy against Gram-negative bacteria is an interesting property useful for the prevention of PJI caused by these bacteria on this potential alternative to the Ti-6Al-4V alloy for orthopedic surgery.

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 on mesoporous 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.

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.

Use of anodized titanium alloy as drug carrier: Ibuprofen as model of drug releasing.

The use of osteoarticular implants has improved the quality of life of millions of patients. In this work nanotubular structures tailored made on Ti6Al4V substrates was used as drug delivery system of ibuprofen as a proof of concept. Three different nanotubular films with different sizes and forms (NT, NT+ and NTb) were analysed. Samples were soaked in a solution of 660 mg ibuprofen/20 mL n-pentane. The ibuprofen release in aqueous medium was evaluated by liquid chromatography reversed-phase (RP-HPLC). To calculate the observed constant k, the amount of ibuprofen released was plotted versus the time using linear regression according to the zero-order, first-order, second-order and Higuchi model. The release of ibuprofen was constant and independent of the concentration. The kinetic constant obtained was 0.021 (NT), 0.022 (NT+) and 0.013 (NTb) being the correlation factor of 0.98 (zero-order) where the maximum correlation factor was reached. These results indicate that the delivery process from NT and NT+ is similar and slower that NTb. In all the cases was inside the therapeutically range. These results showed the potential of these modifications in order to develop implants that can carry different molecules of medical importance.

El problema del control de la polución y las medidas de los contaminantes / No disponible

No disponible

Cambio climático. Una vision global / Climate change. A global overwiew

Este artículo presenta una panorámica de la situación actual del calentamiento global en el Planeta, para después plantear su previsible consecuencia, que no es otra que la de un cambio climático. Todo ello, tratado como un artículo de divulgación científica, orientado a un público amplio. Se han ordenado los hechos y se ha pretendido transmitir un orden lógico. En este tema vamos a encontrar posturas contrapuestas y a veces irreconciliables. Sin embargo, veremos que hay pruebas de un calentamiento global, que puede producir un cambio climático cuyas consecuencias están por definir(AU)

This article presents an overview of the current situation of global warming on the Planet, to later follow with its foreseeable consequences, a climate change. All this is treated as a scientific article, aimed at a wide audience. In this subject we find contradictory and, sometimes, irreconcilable positions. However, there are clear evidences of a global warming, which can produce a climate change whose consequences need to be defined(AU)

Interacción in vivo del Cu(II) con cefotaxima / (Cu)II in vivo interaction with cefotaxime

Este trabajo estudia la reacción del cobre II con una cefalosporina,la cefotoxima, in vivo; los mecanismos catalíticos que implicanla presencia de complejos ternarios, su farmacocinética y su farmacodinamiaque afectan a la actividad del antibiótico. Las diferenciasmás significativas entre las ratas intoxicadas y control fueron observadasen riñón, pulmón e hígado. También hemos estudiado la actividadmicrobicida en Bacillus subtilis CECT 356, Escherichia coliCECT 434, Escherichia coli CECT 616, Staphilococus aureus sppaureus CECT 435, Staphilococus aureus spp aureus CECT 239(AU)

The presence of Cu(II) in penicillin and cephalosporin solutions,has been proved, to promote in vitro the antibiotic degradation tothe corresponding acid derivates. HPLC studies provided anadditional evidence for the reaction mechanism. The mechanisms ofCu(II) catalysis involve a ternary complex. This work was undertakento study the consequences of this degradation in vivo upper thepharmacokinetic, pharmacodynamic and activity of the antibioticcefotaxime. It is one of the most used «third-generation»cephalosporin in the world, this is because of that the interactioncefotaxime-metal deserved our attention. Our results remarked alower concentration of free cefotaxime in blood, liver, spleen, kidney,lung and heart in organs from animals suffering Cu-intoxication.The differences more significant between intoxicated and controlrats were observed in liver, lung and kidney. In addition cefotaximelinked to copper lose most of the microbicidal activity againstbacterial strains of Bacillus subtilis CECT 356, Escherichia coli CECT434, Escherichia coli CECT 616, Staphilococus aureus spp aureusCECT 435, Staphilococus aureus spp aureus CECT 239, in plate tests.It means that cefotaxime would become ineffective as antibiotic inmetal poisoned patients(AU)

Release evaluation of drugs from ordered three-dimensional silica structures.

Cubic mesoporous structures with Ia3d symmetry, such as MCM-48 and large pore Ia3d material (LP-Ia3d), which present different pore size (3.6 and 5.7nm, respectively), have been prepared, characterized and used as drug delivery systems. Ibuprofen and erythromycin have been chosen as drug models for delivery studies. The influence of the pore size at these structures has been studied and the results show that the delivery rate of drugs decreases with the pore size of the matrix. The influence of chemical nature of the pore surface on the delivery process has been also studied. In this case, the hydrophilic pore surface has been modified with hydrocarbon chains (C8 and C18 moieties) and the effect upon drug delivery of hydrophobic drugs like erythromycin has been studied. The results show a noticeable decrease of the delivery rate when the surface of the matrices is modified.