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

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

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

Data supporting the physico-chemical characterization, cellular uptake and cytotoxicity of lipid nanocapsules

This work was supported by the projects MAT2010-20370 and MAT2013-43922-R (European FEDER support included, MICINN, Spain), PI10/02295 (Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria, FEDER funds) and P07-FQM2496, P10-CTS-6270 and P07-FQM3099 (Junta de Andalucia, Spain).The aim of this data article is to provide data for a basic knowledge of the properties of lipid nanocapsules, a new colloidal system with very promising applications in drug delivery. Firstly, we pay attention on how it is possible to determine their surface composition by means of electrokinetics measurements. On the other hand, we provide experimental evidences for a better understanding of the factors that determine the interactions of these nanoparticles with cells as a necessary step to guide the design of the most effective formulations. Additionally, we supply information about encapsulation efficiency of docetaxel, a potent chemotherapy drug, inside nanocapsules supporting the experimental cytotoxicity results of these nanosystems.European Union (EU) MAT2010-20370 MAT2013-43922-RInstituto de Salud Carlos III, Fondo de Investigacion Sanitaria, FEDER funds PI10/02295Junta de Andalucia P07-FQM2496 P10-CTS-6270 P07-FQM3099Spanish Governmen

Ion-Specific Aggregation of Hydrophobic Particles

International audienc

Ion-induced reversibility in the aggregation of hydrophobic colloids

International audienc

Synthesis and Characterization of Lipid Immuno-Nanocapsules for Directed Drug Delivery: Selective Antitumor Activity against HER2 Positive Breast-Cancer Cells

Lipid nanocapsules (LNC) are usually developed as nanocarriers for lipophilic drug delivery. The surface characteristics of these colloidal particles are determinant for a controlled and directed delivery to target tissues with specific markers. We report the development of immuno-nanocapsules, in which some antibody molecules with different immuno-specificity are conjugated to the nanocapsule surface, offering the standardization of a simple method to obtain vectorized nanosystems with specific recognition properties. Nanocapsules were prepared by a solvent-displacement technique, producing an oily core coated by a functional shell of different biocompatible molecules and surface carboxylic groups. Three different antibodies (one a specific HER2 oncoprotein antibody) were conjugated with these nanoparticles by the carbodiimide method, which allows the covalent immobilization of protein molecules through carboxylic surface groups. The immuno-nanocapsules were completely characterized physico-chemically via electrokinetic and colloidal stability experiments, confirming the correct immobilization of these antibody molecules on the colloidal nanoparticles. Also, additional immunological analyses verified that these IgG-LNC complexes showed the expected specific immuno-response. Finally, different healthy and tumoral breast-cell lines were cultured in vitro with Nile-Red-loaded and docetaxel-loaded HER2 immuno-nanocapsules. The results indicate that our immuno-nanocapsules can increase their uptake in HER2 overexpressing tumoral cell lines