Search

This work focuses on the development and evaluation of a dual nanostructured lipid carrier (NLC)/Carbopol®-based hydrogel system as a potential transporter for the topical delivery of curcumin to the skin. Two populations of different sized negatively charged NLCs (P1, 70–90 nm and P2, 300–350 nm) were prepared and characterized by means of dynamic light scattering. NLCs presented an ovoid platelet shape confirmed by transmission electron microscopy techniques. Curcumin NLC entrapment efficiency and release profiles were assessed by HPLC (high pressure liquid chromatography) and spectrophotometric methods. Preservation and enhancement of curcumin (CUR) antioxidant activity in NLCs (up to 7-fold) was established and cell viability assays on fibroblasts and keratinocytes indicated that CUR-NLCs are non-cytotoxic for concentrations up to 10 μM and exhibited a moderate anti-migration/proliferation effect (20% gap reduction). CUR-NLCs were then embedded in a Carbopol®-based hydrogel without disturbing the mechanical properties of the gel. Penetration studies on Franz diffusion cells over 24 h in CUR-NLCs and CUR-NLCs/gels demonstrated an accumulation of CUR in Strat-M® membranes of 22% and 5%, respectively. All presented data support the use of this new dual CUR-NLC/hydrogel system as a promising candidate for adjuvant treatment in topical dermal applications.

The interest of food industry to merchandise natural astaxanthin is growing up. However, it confronts scientific and technological challenges mainly related to its poor water solubility and chemical instability. Here, we present a new quick and efficient green process to simultaneously extract, encapsulate and stabilize astaxanthin from Haematococcus pluvialis. The process is based on the hitherto unexplored combination of supramolecular solvents (SUPRAS), nanostructured liquids generated from amphiphiles through sequential self-assembly and coacervation, and nanostructured lipid carriers (NLCs). These novel nanosystems were characterized by means of dynamic light scattering, AFM and cryoSEM, revealing spherical particles of ∼100 nm. Their antioxidant activity was measured by ORAC (20.6 ± 3.9 μM TE) and α-TEAC (2.92 ± 0.58 µM α-TE) assays and their in vitro capacity to inhibit ROS by DHE probe. Results showed that the SUPRAS-NLCs proposed yield high extraction and encapsulation efficiencies (71 ± 4%) in combination with a remarkable time stability (180 d, 4 °C).

With the rising interest in asymmetric catalysis promoted by earth-abundant elements, a chiral ligand will undoubtedly be the most valuable unit of the catalyst. The first proof of concept of the use of a multitask chiral ligand in an asymmetric assisted tandem catalysis protocol that successively combines metallo- and organocatalytic processes is reported herein. In this protocol, the chiral ligand of the newly designed rare-earth catalyst of the first reaction is converted into a novel chiral organocatalyst for the second transformation by the simple addition of HCl. The observation of some enantioinduction in the tandem sequence—alkyne hydroamination followed by enantioselective Friedel–Crafts alkylation—confirms the relay of the chiral N,N,N′,N′-tetradentate ligand and the importance of its pyridylmethylamine scaffold.

The development of new vascular devices requires to study the effects of materials on blood cells and on coagulation, both in vitro and in vivo. In this study, we have developed a new material by grafting dermatan sulfate (DS) from shark skin onto polyethylene terephthalate (PET). We have evaluated the haemocompatibility of PET-DS material in vitro by measuring thrombin generation, plasma recalcification time, hemolytic activity, and platelet adhesion and in vivo with a model of vascular patch in rat abdominal aorta. In vitro, our results have shown that PET-DS is a nonhemolytic material, able to inhibit thrombin generation and platelet adhesion. In vivo studies by Doppler echographic evaluation 20 days after implantation have shown that the PET-DS patch was integrated in the vessel wall and covered by a layer of cells. In conclusion, PET-DS has good haemocompatibility properties and could be a promising tool for vascular surgery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2001-2009, 2017.

Pharmacology is the science of drugs, which includes their therapeutic use, pharmacokinetics, and toxicology. Delivery of a drug to the blood circulation, and consequently to the site of action within the body to produce a desired therapeutic effect, is the ultimate goal of drug delivery; the when, where, and how of drug delivery being the main questions that must be addressed. Nanopharmacology is concerned with a discovery of new drug entities, nanoscale drug carriers, and selection of pharmaceuticals with a purpose of increasing therapeutic efficacy and reduce toxicity by selective delivery of an active moiety with the aid of nanotechnology. To master drug delivery issues today requires: (i) an overview of the interactions between a substance and a biological system at the molecular level, (ii) to distinguish the peculiarities of the different routes of drug administration, in particular the oral route and the intravenous route, the latter being the most used for nanoparticulate systems (NPS), (iii) to manage the main concepts of materials science at the nanoscale in connection with the biological, pharmacological, and medical constraints of drug therapy, and (iv) an instant view of marketed NPS.

International audience; A novel class of reversible chiral ammonium‐based ionic liquids has been designed and synthesized. These chiral ammonium carbamate salts were quickly obtained by adding 1 atmosphere of CO2 gas to chiral silylated amines, easily prepared at gram scale and in some steps from natural amino acids as bio‐renewable substrates. Some physical properties of these reversible chiral ionic liquids such as reversibility temperature, thermal degradation, miscibility, and stability have been determined. The spectroscopic characteristics of the silylated amine and ionic liquid states have also been compared. The properties of reversibility, chirality, and ease of preparation should make these silylamine‐ionic liquid phases as promising solvents and/or catalysts for several applications, especially in asymmetric catalysis fields.

The development of new vascular devices requires to study the effects of materials on blood cells and on coagulation, both in vitro and in vivo. In this study, we have developed a new material by grafting dermatan sulfate (DS) from shark skin onto polyethylene terephthalate (PET). We have evaluated the haemocompatibility of PET-DS material in vitro by measuring thrombin generation, plasma recalcification time, hemolytic activity, and platelet adhesion and in vivo with a model of vascular patch in rat abdominal aorta. In vitro, our results have shown that PET-DS is a nonhemolytic material, able to inhibit thrombin generation and platelet adhesion. In vivo studies by Doppler echographic evaluation 20 days after implantation have shown that the PET-DS patch was integrated in the vessel wall and covered by a layer of cells. In conclusion, PET-DS has good haemocompatibility properties and could be a promising tool for vascular surgery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2001-2009, 2017.

Metal–organic frameworks (MOFs) are coordination polymers of interest for biomedical applications. Of particular importance, nanoparticles made of iron(III) trimesate (MIL-100, MIL standing for Material Institut Lavoisier) (nanoMOFs) can be conveniently synthesised under mild and green conditions. They were shown to be biodegradable, biocompatible and efficient to encapsulate a variety of active molecules. We have addressed here the challenges to encapsulate a highly hydrophilic anticancer prodrug, phosphated gemcitabin (Gem-MP) known for its instability and inability to bypass cell membranes. MIL-100 nanoMOFs acted as efficient “nanosponges”, soaking Gem-MP from its aqueous solution with almost perfect efficiency (>98%). Maximal loadings reached ∼30 wt% reflecting the strong interaction between the drug and the iron trimesate matrices. Neither degradation nor loss of crystalline structure was observed after the loading process. Storage of the loaded nanoMOFs in water did not result in drug release over three days. However, Gem-MP was released in media containing phosphates, as a consequence to particle degradation. Drug-loaded nanoMOFs were effective against pancreatic PANC-1 cells, in contrast to free drug and empty nanoMOFs. However, an efflux phenomenon could contribute to reduce the efficacy of the nanocarriers. Size optimization and surface modification of the nanoMOFs are expected to further improve these findings.

International audience

La presente tesis doctoral describe el desarrollo de procesos químicos medioambientalmente sostenibles, incidiendo en la búsqueda de nuevas estrategias de síntesis y recuperación de catalizadores homogéneos con objeto de extender su vida media. Desde otra vertiente, se hace hincapié en el diseño de catalizadores multifuncionales para ser aplicados en reacciones dominó. En ambos casos se ha estudiado la aplicabilidad de diferentes catalizadores de oro basados tanto en nanopartículas metálicas como en sales de Au(I) y Au(III), para generar productos de interés en la industria química y farmacéutica. En los diferentes capítulos se abordan los siguientes contenidos: - La síntesis de complejos de oro (I) coordinados con ligandos fosfina y su aplicación en la hidroalcoxilación intermolecular de alquinos para formar éteres de enol y acetales. - La transformación de alquinos en acetales y tioacetales cíclicos catalizada por el sistema catalítico AuPPh3Cl/AgBF4. Este tipo de reacciones nos permite sintetizar una molécula con aroma a esencia de naranja. - La formación de acetales de alto valor añadido a partir de aldehídos y glicerol puro o mezclas glicerol-agua empleando ácidos de Brønsted sólidos (zeolitas y resinas) y ácidos de Lewis basados en Au. Además en algún caso se hace posible recuperar y reutilizar este catalizador. - El estudio de diferentes rutas "one-pot" para la síntesis de derivados bencimidazólicos en presencia de un catalizador sólido bifuncional. La deposición de un metal (nanopartículas de oro o paladio) sobre un soporte básico permite la síntesis de un bencimidazol con actividad antiviral (anti-VIH-1) mediante una transformación secuencial de cuatro pasos. Además, se llevó a cabo la síntesis del derivado dibencimidazólico Ho33342 con propiedades anticancerígenas mediante una ruta sintética basada en el empleo de los mismos catalizadores sólidos metálicos., Rodriguez Ruiz, V. (2010). Catalizadores de oro en reacciones de hidroalcoxilación, acetalización y reacciones integradas en procesos "one-pot": una aproximación eficiente a la química sostenible [Tesis doctoral no publicada]. Universitat Politècnica de València. doi:10.4995/Thesis/10251/8539.

This Perspective article provides an overview of the recent advancements in the field of intra- and inter-molecular C–N, C–O and C–P bond formation by hydroamination, hydroalkoxylation, hydrophosphination, hydrophosphonylation or hydrophosphinylation of unactivated alkenes, including allenes, 1,3-dienes and strained alkenes, promoted by (chiral) homogeneous catalysts based on earth abundant elements of the s and p blocks, the first row transition metals and the rare-earth metals. The relevant literature from 2009 until late 2014 has been covered.

A comparison of the properties of the highly porous iron(III) trimesate MIL-100 nanoparticles (nano-MOFs) obtained through a hydrofluoric acid-free ‘green’ synthesis route with those obtained from the ‘conventional’ HF procedure is reported, in terms of particle crystallinity, porosity and space time yield (STY). It appears that the use of more concentrated reaction conditions have led to the highest STY values while maintaining a good degree of purity. As the fluorinated nano-MOFs, the F-free solids are able to encapsulate high payloads of a challenging antiviral drug, azidothymidine triphosphate, and to release it on a progressive manner. Furthermore, the F-free nano-MOFs were shown to be highly taken up by macrophages, targets for antiviral therapy, without inducing any detectable toxic side effects. This study opens up novel perspectives for the large-scale synthesis of ‘green’ MIL-100 nano-MOFs for biomedical applications. Supplementary information will be available at http://www.icevirtuallibrary.com/upload/10.1680gmat.13.00001_SupplementaryInformation.pdf