Characterization of Different Functionalized Lipidic Nanocapsules as Potential Drug Carriers

Lipid nanocapsules (LNC) based on a core-shell structure consisting of an oil-filled core with a surrounding polymer layer are known to be promising vehicles for the delivery of hydrophobic drugs in the new therapeutic strategies in anti-cancer treatments. The present work has been designed as basic research about different LNC systems. We have synthesized—and physico-chemically characterized—three different LNC systems in which the core was constituted by olive oil and the shell by different phospholipids (phosphatidyl-serine or lecithin) and other biocompatible molecules such as Pluronic® F68 or chitosan. It is notable that the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this work and was designed to generate an enriched carboxylic surface. This carboxylic layer is meant to link specific antibodies, which could facilitate the specific nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl-serine in their shell have also been used in this work to form immuno-nanocapsules containing a polyclonal IgG against a model antigen (C-reactive protein) covalently bounded by means of a simple and reproducible carbodiimide method. An immunological study was made to verify that these IgG-LNC complexes showed the expected specific immune response. Finally, a preliminary in vitro study was performed by culturing a breast-carcinoma cell line (MCF-7) with Nile-Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile- Red molecule in a process dependent on the surface properties of the nanocarriers

Smart Drug-Delivery Systems for Cancer Nanotherapy

Despite all the advances achieved in the field of tumor-biology research, in most cases conventional therapies including chemotherapy are still the leading choices. The main disadvantage of these treatments, in addition to the low solubility of many antitumor drugs, is their lack of specificity, which explains the frequent occurrence of serious side effects due to nonspecific drug uptake by healthy cells. Progress in nanotechnology and its application in medicine have provided new opportunities and different smart systems. Such systems can improve the intracellular delivery of the drugs due to their multifunctionality and targeting potential. The purpose of this manuscript is to review and analyze the recent progress made in nanotherapy applied to cancer treatment. First, we provide a global overview of cancer and different smart nanoparticles currently used in oncology. Then, we analyze in detail the development of drug-delivery strategies in cancer therapy, focusing mainly on the intravenously administered smart nanoparticles with protein corona to avoid immune-system clearance. Finally, we discuss the challenges, clinical trials, and future directions of the nanoparticle-based therapy in cancer.Comment: Preprint version, 25 pages, 7 figures, 3 tables. Authors thank to Bentham Science the posibility of deposit the ACCEPTED VERSION of the peer-reviewed article after 12 months of publication on journal web site on arXiv repository. The published manuscript is available at EurekaSelect via https://www.eurekaselect.com/openurl/content.php?genre=article&doi=10.2174/138945011766616052714254

Smart drug-delivery systems for cancer nanotherapy

Authors thanks Bentham Sciencew for allow the deposit of the ACCEPTED VERSION of this peer-reviewed article in this institutional repository. Commons License CC BY-NC-ND 4.0 - Attribution-NonCommercial-NoDerivatives 4.0 International. The published manuscript is available at EurekaSelect via https://www.eurekaselect.com/openurl/content.php? genre=article&doi=10.2174/1389450117666160527142544Despite all the advances achieved in the field of tumor-biology research, in most cases conventional therapies including chemotherapy are still the leading choices. The main disadvantage of these treatments, in addition to the low solubility of many antitumor drugs, is their lack of specificity, which leads to the occurrence of severe side effects due to nonspecific drug uptake by healthy cells. Progress in nanotechnology and its application in medicine have provided new opportunities and different smart systems. Such systems can improve the intracellular delivery of the drugs due to their multifunctionality and targeting potential. The purpose of this manuscript is to review and analyze the recent progress made in cancer nanotherapy. First, we provide a global overview of cancer and different smart nanoparticles currently used in oncology. Then, we analyze in detail the development of drug-delivery strategies in cancer therapy, focusing mainly on the intravenously administered smart nanoparticles with protein corona to avoid immune-system clearance. Finally, we discuss the challenges, clinical trials, marketed nanomedicines and future directions of the nanotherapy applied to cancer treatment.This work was supported by the projects MAT2013-43922-R, MAT2015-63644-C2-2-R, (European FEDER support included, MINECO Spain), PI-0533-2014 (Fundación Progreso y Salud/Janssen Cilag, Junta de Andalucía, Spain) and P07-FQM2496, P10-CTS-6270 and P07- FQM3099 (Junta de Andalucía, Spain)

Novel Drug Delivery System Based on Docetaxel-Loaded Nanocapsules as a Therapeutic Strategy Against Breast Cancer Cells

In the field of cancer therapy, lipid nanocapsules based on a core-shell structure are promising vehicles for the delivery of hydrophobic drugs such as docetaxel. The main aim of this work was to evaluate whether docetaxel-loaded lipid nanocapsules improved the anti-tumor effect of free docetaxel in breast cancer cells. Three docetaxel-loaded lipid nanocapsules were synthesized by solvent displacement method. Cytotoxic assays were evaluated in breast carcinoma (MCF-7) cells treated by the sulforhodamine B colorimetric method. Cell cycle was studied by flow cytometry and Annexin V-FITC, and apoptosis was evaluated by using propidium iodide assays. The anti-proliferative effect of docetaxel appeared much earlier when the drug was encapsulated in lipid nanoparticles than when it was free. Docetaxel-loaded lipid nanocapsules significantly enhanced the decrease in IC50 rate, and the treated cells evidenced apoptosis and a premature progression of the cell cycle from G(1) to G(2)-M phase. The chemotherapeutic effect of free docetaxel on breast cancer cells is improved by its encapsulation in lipid nanocapsules. This approach has the potential to overcome some major limitations of conventional chemotherapy and may be a promising strategy for future applications in breast cancer therapy

Empty Urbanism: the bursting of the Spanish housing bubble

The depth of the Spanish housing crisis manifests itself in the collapse of construction activity and in the amount of housing and land stocks. The geography of the crisis shows its widespread nature, and the intensity of the previous bubble explains spatial differences. Resulting from this collapse are some problematic areas of 'empty urbanism'. An enormous land bubble, emerging from the peculiar Spanish urban development model, was a key factor in the impacts - caused by the crisis - on the territory and land-use plans. The crisis has demonstrated the unsustainability of this and the urgency of change in the existing land-use plans

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Estabilidad coloidal de interfases estructuradas : aplicación a inmunosensores

Este trabajo de investigación se enmarca en el ámbito de la física de fluidos coloidales. el objetivo fundamental se ha centrado en el estudio tanto de la absorción del fragmento (f(ab')2 como de un lípido (diestearil dimetil amonio) sobre partículas polimétricas y el análisis de la estabilidad coloidal de las dispersiones formadas. en esta tesis se desarrollan cinco líneas de investigación, que no son en ningún caso independientes: * síntesis y caracterización de nuevos coloides polimétricos. * absorción del fragmento proteico f(ab')2 y su co adsorción con albúmina sobre estos coloides. * análisis de la estabilidad coloidal de las partículas de látex sensibilizadas, mediante ensayos de co adsorción con un lípido sintético. * seguimiento óptico de la aglutinación de partículas coloidales. * estudio de las variables experimentales que pueden afectar al resultado final de un inmuno ensayo de látex.Este trabajo de investigación se enmarca en el ámbito de la física de fluidos coloidales. el objetivo fundamental se ha centrado en el estudio tanto de la absorción del fragmento (f(ab')2 como de un lípido (diestearil dimetil amonio) sobre partículas polimétricas y el análisis de la estabilidad coloidal de las dispersiones formadas. en esta tesis se desarrollan cinco líneas de investigación, que no son en ningún caso independientes: * síntesis y caracterización de nuevos coloides polimétricos. * absorción del fragmento proteico f(ab')2 y su co adsorción con albúmina sobre estos coloides. * análisis de la estabilidad coloidal de las partículas de látex sensibilizadas, mediante ensayos de co adsorción con un lípido sintético. * seguimiento óptico de la aglutinación de partículas coloidales. * estudio de las variables experimentales que pueden afectar al resultado final de un inmuno ensayo de látex