Drug delivery properties of macroporous polystyrene solid foams

Purpose. Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. Methods. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Results. Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. Conclusions. Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-timePostprint (published version

Biotinylated polyurethane-urea nanoparticles for targeted theranostics in human hepatocellular carcinoma

Over the past years, significant efforts have been devoted to explore novel drug delivery and detection strategies for simultaneous therapy and diagnostics. The development of biotinylated polyurethane-urea nanoparticles as theranostic nanocarriers for targeted drug and plasmid delivery, for fluorescence detection of human hepatocellular carcinoma cells, is described herein. These targeted nanoparticles are specifically designed to incorporate biotin into the polymeric matrix, since many tumor types overexpress receptors for biotin as a mechanism to boost uncontrolled cell growth. The obtained nanoparticles were spherical, exhibited an average diameter ranging 110–145 nm, and showed no cytotoxicity in healthy endothelial cells. Biotinylated nanoparticles are selectively incorporated into the perinuclear and nuclear area of the human hepatocellular carcinoma cell line, HepG2, in division, but not into growing, healthy, human endothelial cells. Indeed, the simultaneous incorporation of the anticancer drugs, phenoxodiol or sunitinib, together with plasmid DNA encoding green fluorescent protein, into these nanoparticles allows a targeted pharmacological antitumor effect and furthermore, selective transfection of a reporter gene, to detect these cancer cells. The combined targeted therapy and detection strategy described here could be exploited for liver cancer therapy and diagnostics, with a moderate safety profile, and may also be a potential tool for other types of cancer.Spain. Ministerio de Educación y CienciaDGI (Spain) (CTQ 2011-29336-C03/PPQ)Catalonia (Spain). Departament d'Universitats, Recerca i Societat de la Informació (DURSI) (Grant 2009 SGR-961)CIBER-BB

Cubic Liquid Crystalline Structures in diluted, concentrated and highly concentrated emulsions for topical application: influence on drug release and human skin permeation

Novel emulsions with a nanostructured continuous phase have been proposed as controlled drug delivery systems to enhance topical delivery of active ingredients avoiding systemic effects. In this study, oil-in-water (O/W) emulsions with two surfactant/water (S/W) weight ratios of 40:60 and 35:65, and oil concentrations of 10 wt% (diluted emulsion), 40 wt% (concentrated emulsion) and 85 wt% (highly concentrated emulsion) have been investigated to identify the presence of liquid crystalline structures and their influence on drug release and skin permeation. The emulsions have been characterized in terms of visual appearance, rheology and drug release. The presence of cubic liquid crystalline structures in emulsions with S/W 40:60 was confirmed by small angle X-ray scattering (SAXS). Rheology results showed a markedly different behaviour in emulsions with S/W 40:60 compared with nonstructured emulsions. A model drug, diclofenac sodium (DS) was successfully incorporated in the emulsions. DS release was studied with hydrophilic and lipophilic membranes, and the amount of DS in the receptor solution was significantly lower in the formulations containing cubic liquid structures. An in vitro skin permeation study with dermatomed human skin showed that emulsions with a nanostructured continuous phase are suitable formulations for topical delivery with DS retention in skin layers. The results indicate that the amount of drug retained in skin structures may be tuned by modification of liquid crystal concentration and emulsion structure

Análisis de aguas residuales con fines epidemiológicos: aplicaciones a la estimación del consumo de sustancias de abuso y en salud pública en general. Red española ESAR-Net

En este artículo se presenta la metodología de análisis de aguas residuales con fines epidemiológicos (wastewater-based epidemiology, WBE) y su potencial para abordar diversos aspectos relacionados con la salud pública. Esta metodología permite obtener datos a una escala temporal y espacial relativamente pequeña (típicamente datos diarios-semanales sobre un municipio) de hábitos de consumo de sustancias de abuso, ilegales (como la cocaína o el cannabis) o legales (como el alcohol) a través de la determinación de biomarcadores de consumo (el compuesto original no metabolizado o alguno de sus metabolitos) en el agua residual. Aparte de discutir los fundamentos, ventajas y limitaciones de WBE, se comentan los precedentes más relevantes a nivel internacional, y las actividades más destacables en España en este ámbito. Finalmente, se exponen, los objetivos de la Red Española de Análisis de Aguas Residuales con Fines Epidemiológicos (ESAR-Net), una "Red de Excelencia" que agrupa a investigadores españoles con amplia experiencia en el área de WBE, así como las perspectivas de futuro de esta metodología puede tener para mejorar las competencias de la Salud Pública en España

El análisis de aguas residuales con fines epidemiológicos: presente y futuro en España

El análisis de aguas residuales con fines epidemiológicos es actualmente una herramienta fiable y complementaria a las metodologías basadas en indicadores tradicionales para el control de diferentes sustancias entre las que cabe destacar las drogas. Si bien varios países europeos la utilizan como herramienta de trabajo para la monitorización de drogas de abuso, en España su uso se limita principalmente a estudios realizados por diferentes grupos de investigación, tal y como se describe en el caso práctico puesto de ejemplo en el artículo. Sin embargo, el potencial de la metodología ha quedado evidenciado en los estudios científicos llevados a cabo tanto a nivel español como internacional y, aunque son necesarios más estudios para llegar a conocer todo su potencial, se prevé pueda ser incorporada como herramienta de trabajo complementaria a las que habitualmente se utilizan. En este sentido, la Red Española de Análisis de Aguas Residuales (ESAR-Net), creada en 2017 y formada por diferentes grupos de investigación españoles, pretende contribuir al conocimiento y aplicación de esta metodología en España a través de actividades científicas y de divulgación.Este estudio ha sido financiado por la Agencia Estatal de Investigación (AEI) a través del programa Redes de Excelencia (CTM2016-81935-REDT)S

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Low-energy nano-emulsification approach as a simple strategy to prepare positively charged ethylcellulose nanoparticles

Positively charged ethylcelulose nanoparticles have been obtained from alkylamidoammonium/Span 80 based nano-emulsion templates. Oil-in-water polymeric nano-emulsions form in a broad range of oil-to-surfactant ratios and water contents above 75 wt% by a low-energy method at 25 °C. Nano-emulsions with a water content of 90 wt% showed droplet sizes typically below 300 nm and high positive zeta potential values (∼55 mV). If oleylamine is added to the system, smaller droplet sizes and higher zeta potential values (∼66 mV) are obtained, but the stability of the nano-emulsions decreases. Although these nano-emulsions are destabilized by creaming, the period of stability is large enough to allow nanoparticle preparation by solvent evaporation. Polymeric nanoparticles obtained show a globular core-shell-like morphology, with mean diameters of around 250 nm. The surface charge of the nanoparticles is similar to that of the nano-emulsion template and remains positive after 24 h dialysis, suggesting slow desorption kinetics of the alkylamidoammonium from the nanoparticle surface. These results indicate that the proposed nano-emulsion approach is a good strategy for the preparation of positively charged nanoparticles from nonionic ethylcellulose polymers. © 2018 Elsevier LtdFinancial support from MINECO (grant CTQ2011-29336-C03-01 ) and Generalitat de Catalunya (grant 2009SGR-961 ) is acknowledged. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund . S.L. is grateful to CIBER-BBN for a research scholarship. The DLS and Zeta potential analyses have been performed at the Nanostructured Liquid Characterization Unit, located at the Institute of Advanced Chemistry of Catalonia (IQAC), belonging to the Spanish National Research Council (CSIC) and affiliated to the NANBIOSIS ICTS of the CIBER-BBN. Prof. M.L. García of the Dept. of Physical-Chemistry at the Univ. of Barcelona is gratefully acknowledged for facilitating the use of TurbiscanLab® Expert. GPC analysis has been carried out at the Unitat de Tècniques Separatives i Síntesi de Pèptids of the CCiT-UB (University of Barcelona). Colorcon and Bonderalia S.A./Quimivita S.A. are gratefully acknowledged for the gift of ethylcellulose and ricinoleamidopropyltrimonium methosulfate respectively. Appendix APeer reviewe

Drug delivery properties of macroporous polystyrene solid foams

Purpose. Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. Methods. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Results. Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. Conclusions. Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-tim

Rosmarinic Acid-Loaded Polymeric Nanoparticles Prepared by Low-Energy Nano-Emulsion Templating: Formulation, Biophysical Characterization, and In Vitro Studies

Rosmarinic acid (RA), a caffeic acid derivative, has been loaded in polymeric nanoparticles made up of poly(lactic-co-glycolic acid) (PLGA) through a nano-emulsion templating process using the phase-inversion composition (PIC) method at room temperature. The obtained RA-loaded nanoparticles (NPs) were colloidally stable exhibiting average diameters in the range of 70-100 nm. RA was entrapped within the PLGA polymeric network with high encapsulation efficiencies and nanoparticles were able to release RA in a rate-controlled manner. A first-order equation model fitted our experimental data and confirmed the prevalence of diffusion mechanisms. Protein corona formation on the surface of NPs was assessed upon incubation with serum proteins. Protein adsorption induced an increase in the hydrodynamic diameter and a slight shift towards more negative surface charges of the NPs. The radical scavenging activity of RA-loaded NPs was also studied using the DPPH·assay and showed a dose-response relationship between the NPs concentration and DPPH inhibition. Finally, RA-loaded NPs did not affect the cellular proliferation of the human neuroblastoma SH-SY5Y cell line and promoted efficient cellular uptake. These results are promising for expanding the use of O/W nano-emulsions in biomedical applications.The authors acknowledge the Agencia Estatal de Investigación for funding (Project CTQ2017-84998-P) and the Instituto de Salud Carlos III (ISCIII) (CB06/01/1058). CIBER-BBN is an initiative funded by the VI National R + D + I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER actions and financed by ISCIII with assistance from the European Regional Development Fund.Peer reviewe

Polyamide fabric coated with a dihydroxyacetone-loaded chitosan hydrogel for a cosmeto-textile application

Cosmeto-textiles, which allow the administration of molecules when in contact with the skin, are increasingly being developed by cosmetic industries. We have designed an innovative approach for cosmeto-textile products, based on the impregnation of textile fibers with chitosan hydrogels, which have been cross-linked with genipin and loaded with dihydroxyacetone, which is an active component that induces sunless tanning. Dihydroxyacetone-loaded chitosan hydrogels have been prepared and characterized by means of cryogenic scanning electron microscopy (cryo-SEM). The images showed that genipin cross-linking decreases the mesh distance of hydrogels. The release of dihydroxyacetone from these cross-linked genipin chitosan hydrogels has been studied by a dialysis membrane method. These dihydroxyacetone-loaded chitosan hydrogels have been incorporated to polyamide textiles by a simple padding technique. The presence of dihydroxyacetone on these textiles has been detected by hyperspectral imaging on a dark field high resolution optical microscope. Finally, the performance of fabrics as cosmeto-textiles, with a tanning effect, has been evaluated by skin-colorimetry measured with an evaluation panel of 10 people. The results have demonstrated that dihydroxyacetone-loaded textiles produce a tanning effect on skin, and incorporation of dihydroxyacetone-loaded chitosan hydrogels into polyamide fabrics represents a friendly and appropriate strategy to obtain a cosmeto-textile with tanning effect. © The Author(s) 2019.The authors acknowledge financial support from CDTI (INNPACTO program), grant IPT-300000-2010-0026. The optical microscope observations have been performed by the Nanostructured Liquid Characterization Unit, located at the Institute of Advanced Chemistry of Catalonia (IQAC), belonging to the Spanish National Research Council (CSIC) and affiliated to the NANBIOSIS ICTS of the Biomedical Networking Center (CIBER-BBN).Peer reviewe