La vida de las mujeres en las ciudades. Narcea, Madrid (1998). Chris Booth.Jane Darkey Susan Veandie (Coord.)

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El silencio administrativo: nuevo tratamiento legal (Ley 30/1992).

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Smart Mesoporous Nanomaterials for Antitumor Therapy

The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc.) or external (temperature, light, magnetic field, etc.) stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment

Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer

Introduction: Nanocarriers have emerged as a powerful alternative for cancer therapy.Indeed, they are promising candidates to tackle the acquired resistance of surviving cells against antiproliferative drugs – the so-called multidrug resistance (MDR) phenomenon – which has arisen as one of the major clinical issues of chemotherapy. Among nanocarriers, this review focuses on the recent approaches based on tailored mesoporous silica nanoparticles (MSNs) that could overcome this problem. Areas covered: Herein we summarize the current efforts developed to provide MSNbased nanosystems of enhanced dual therapeutic action against diseased cells. This can be accomplished by three main approaches: i) increasing nanosystems’ killing capability towards particular cells by enhancing both recognition and specificity; ii)increasing the apoptotic effect throughout co-delivery of several drugs; or iii)combining drug delivery with apoptosis induced by physical methods. Expert Opinion: The development of multifunctional nanosystems able to exert the optimal therapeutic action through the minimal administration constitutes a major challenge in nanomedicine. Recent developments in advanced MSN-based platforms for drug delivery represent promising avenues in the management of MDR associated with cancer therapy. All strategies discussed in this manuscript demonstrate improvements against difficult-to-treat tumors

Mesoporous Silica Nanoparticles for Drug Delivery: Current Insights

This manuscript reviews the recent progress on mesoporous silica nanoparticles as drug delivery systems. Their intrinsic structural, textural and chemical features permit to design versatile multifunctional nanosystems with the capability to target the diseased tissue and release the cargo on demand upon exposition to internal or external stimuli. The degradation rate of these nanocarriers in diverse physiological fluids is overviewed obeying their significance for their potential translation towards clinical applications. To conclude, the balance between the benefits and downsides of this revolutionary nanotechnological tool is also discussed

Recent advances in mesoporous silica nanoparticles for antitumor therapy: our contribution

Since 2001, when our research group proposed for the first time MCM-41 as a drug release system, the scientific community has demonstrated a growing interest in mesoporous silica nanoparticles (MSNs) for their revolutionary potential in nanomedicine. Among the diverse pathologies that can be treated with MSNs, cancer has received increasing attention. MSNs can be loaded with large amounts of therapeutic cargoes and once intravenously administrated preferentially accumulate in solid tumours via the enhanced permeation and retention (EPR) effect. Herein we report the recent developments achieved by our research group as a pioneer in this field, highlighting: the design of sophisticated MSNs as stimuli-responsive drug delivery systems to release the entrapped cargo upon exposure to a given stimulus while preventing the premature release of highly cytotoxic drugs before reaching the target; transporting non-toxic prodrugs and the enzyme responsible for its conversion into cytotoxic agents into the same MSNs; improving the selectivity and cellular uptake by cancer cells by active targeting of MSNs; increasing the penetration of MSNs within the tumour mass, which is one of the major challenges in the use of NPs to treat solid tumours

Tuning mesoporous silica dissolution in physiological environments: a review

Matrix degradation has a major impact on the release kinetics of drug delivery systems. Regarding ordered mesoporous silica materials for biomedical applications, their dissolution is an important parameter that should be taken into consideration. In this paper, we review the main factors that govern the mesoporous silica dissolution in physiological environments. We also provide the necessary knowledge to researchers in the area for tuning the dissolution rate of those matrices, so the degradation could be controlled and the material behaviour optimised

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

Amine-Functionalized Mesoporous Silica Nanoparticles: A New Nanoantibiotic for Bone Infection Treatment

This manuscript reports an effective new alternative for the management of bone infection by the 5 development of an antibiotic nanocarrier able to penetrate bacterial biofilm, thus enhancing antimicrobial effectiveness. This nanosystem, also denoted as “nanoantibiotic”, consists in mesoporous silica nanoparticles (MSNs) loaded with an antimicrobial agent (levofloxacin, LEVO) 10 and externally functionalized with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (DAMO) as targeting agent. This amine functionalization provides MSNs of positive charges, which improves the affinity towards the negatively charged bacteria wall and biofilm. Physical and 15 chemical properties of the nanoantibiotic were studied using different characterization techniques, including Xray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption porosimetry, elemental chemical analysis, dynamic light scattering (DLS), zeta (� )-potential 20 and solid-state nuclear magnetic resonance (NMR). “In vial” LEVO release profiles and the in vitro antimicrobial effectiveness of the different released doses were investigated. The efficacy of the nanoantibiotic against a S. aureus biofilm was also determined, showing the practically total 25 destruction of the biofilmdue to the high penetration ability of the developed nanosystem. These findings open up promising expectations in the field of bone infection treatment

Selective topotecan delivery to cancer cells by targeted pH-sensitive mesoporous silica nanoparticles

Topotecan (TOP), a water-soluble derivative of camptothecin, is a potent antitumor agent that is receiving growing attention for the treatment of several types of cancer. However, one of the major constraints in the clinical use of this drug is its inactivation at the physiological pH of 7.4. Mesoporous silica nanoparticles (MSNs) constitute promising nanocarriers to circumvent this issue. Herein TOP has been encapsulated into MSNs and the nanosystem has been provided with selectivity towards tumor cells, which permits releasing the active form of the molecule at the acidic cell compartments (endo/lysosomes; pH <= 5.5) following nanoparticle internalization. For this purpose, MSNs have been coated with a multifunctional gelatin shell that: (i) protects TOP from hydrolysis and prevents its premature release; (ii) acts as a pH-sensitive layer; and (iii) provides multiple anchoring points for the grafting of targeting ligands, such as folic acid (FA), for selective internalization in tumor cells. In vitro tests demonstrate that cancer cells that overexpress membrane cell surface markers with affinity towards FA, internalize a higher percentage of nanoparticles than healthy cells, which do not overexpress such markers. Moreover, the nanosystems are efficient at killing tumor cells, whereas they do not decrease the viability of normal cells. In contrast, free TOP failed to kill both cell lines, which can be ascribed to the inactivation of the drug. This novel nanodevice constitutes a step forward toward the design of novel weapons to fight against cancer