Click Chemistry with Polymers, Dendrimers, and Hydrogels for Drug Delivery

This is a post-peer-review, pre-copyedit version of an article published in Pharmaceutical Research. The final authenticated version is available online at: https://doi.org/10.1007/s11095-012-0683-yDuring the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug deliveryThis work was financially supported by the Spanish Ministry of Science and Innovation (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037)S

Dually sensitive dextran-based micelles for methotrexate delivery

Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug

Programmed assembly of polymer-DNA conjugate nanoparticles with optical readout and sequence-specific activation of biorecognition

Soft micellar nanoparticles can be prepared from DNA conjugates designed to assemble via base pairing such that strands containing a polymer corona and a cholesterol tail generate controlled supramolecular architecture. Functionalization of one DNA conjugate strand with a biorecognition ligand results in shielding of the ligand when in the micelle, while encoding of the DNA sequences with overhangs allows supramolecular unpacking by addition of a complementary strand and sequence-specific unshielding of the ligand. The molecular assembly/disassembly and ‘on–off’ switch of the recognition signal is visualized by FRET pair signalling, PAGE and a facile turbidimetric binding assay, allowing direct and amplified readout of nucleic acid sequence recognition

Comprensión lectora y rendimiento académico en el área de comunicación en estudiantes del cuarto grado de secundaria de la Institución Educativa N° 20066 “Simón Bolívar” Oyón - 2014

Nuestro trabajo de Investigación, tiene por objetivo determinar la relación entre la Comprensión lectora y el Rendimiento académico en el área de comunicación en los estudiantes del cuarto grado de secundaria de la Institución Educativa Nº 20066 “Simón Bolívar” Oyón– 2014. La investigación es cuantitativa no experimental, se realizó como un estudio transeccional descriptivo correlacional. La muestra fue probabilística aleatoria simple, se obtuvo de una población de 99 estudiantes de ambos sexos, quedando una muestra de 79 alumnos de la Institución Educativa N° 20066 “Simón Bolívar” Oyón - 2014. Se administró un cuestionario sobre comprensión de textos a los estudiantes, y para las pruebas de hipótesis, se usó el estadístico de correlación de Pearson. Al concluir el trabajo de investigación es importante destacar que al aplicar los instrumentos se comprobó que existe relación moderada fuerte positiva entre la Comprensión lectora y el Rendimiento académico en el área de comunicación, en los estudiantes del cuarto grado de secundaria de la Institución Educativa Nº 20066 “Simón Bolívar – Oyón 2014

Dictamen con objeto de analizar la concurrencia de un delito contra la seguridad en el trabajo. Articulos 316 y siguientes del Codigo Penal

El dictamen trata de analizar un posible delito contra los derechos de los trabajadores tipificado en los articulos 316 y siguientes del Codigo Pena

Polyion complex (PIC) particles:Preparation and biomedical applications

AbstractOppositely charged polyions can self-assemble in solution to form colloidal polyion complex (PIC) particles. Such nanomaterials can be loaded with charged therapeutics such as DNA, drugs or probes for application as novel nanomedicines and chemical sensors to detect disease markers. A comprehensive discussion of the factors affecting PIC particle self-assembly and their response to physical and chemical stimuli in solution is described herein. Finally, a collection of key examples of polyionic nanoparticles for biomedical applications is discussed to illustrate their behaviour and demonstrate the potential of PIC nanoparticles in medicine

Poly(triazolyl methacrylate) glycopolymers as potential targeted unimolecular nanocarriers

© The Royal Society of Chemistry 2019.Synthetic glycopolymers are increasingly investigated as multivalent ligands for a range of biological and biomedical applications. This study indicates that glycopolymers with a fine-tuned balance between hydrophilic sugar pendant units and relatively hydrophobic polymer backbones can act as single-chain targeted nanocarriers for low molecular weight hydrophobic molecules. Non-covalent complexes formed from poly(triazolyl methacrylate) glycopolymers and low molecular weight hydrophobic guest molecules were characterised through a range of analytical techniques-DLS, SLS, TDA, fluorescence spectroscopy, surface tension analysis-and molecular dynamics (MD) modelling simulations provided further information on the macromolecular characteristics of these single chain complexes. Finally, we show that these nanocarriers can be utilised to deliver a hydrophobic guest molecule, Nile red, to both soluble and surface-immobilised concanavalin A (Con A) and peanut agglutinin (PNA) model lectins with high specificity, showing the potential of non-covalent complexation with specific glycopolymers in targeted guest-molecule delivery.Peer reviewedFinal Published versio

Site-selective and rewritable labeling of DNA through enzymatic, reversible, and click chemistries

International audienc