214 research outputs found
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
Stimuli‐Responsive Delivery of Antimicrobial Peptides Using Polyelectrolyte Complexes
[Abstract] Antimicrobial peptides (AMPs) are antibiotics with the potential to address antimicrobial resistance. However, their translation to the clinic is hampered by issues such as off-target toxicity and low stability in biological media. Stimuli-responsive delivery from polyelectrolyte complexes offers a simple avenue to address these limitations, wherein delivery is triggered by changes occurring during microbial infection. The review first provides an overview of pH-responsive delivery, which exploits the intrinsic pH-responsive nature of polyelectrolytes as a mechanism to deliver these antimicrobials. The examples included illustrate the challenges faced when developing these systems, in particular balancing antimicrobial efficacy and stability, and the potential of this approach to prepare switchable surfaces or nanoparticles for intracellular delivery. The review subsequently highlights the use of other stimuli associated with microbial infection, such as the expression of degrading enzymes or changes in temperature. Polyelectrolyte complexes with dual stimuli-response based on pH and temperature are also discussed. Finally, the review presents a summary and an outlook of the challenges and opportunities faced by this field. This review is expected to encourage researchers to develop stimuli-responsive polyelectrolyte complexes that increase the stability of AMPs while providing targeted delivery, and thereby facilitate the translation of these antimicrobials.P.F.-T. thanks the University of Birmingham for the John Evans Fellowship and the Spanish Ministerio de Educación, Cultura y Deporte for a Beat-riz Galindo Award [BG20/00213]. F.C. acknowledges the National Healthand Medical Research Council Leadership Investigator Research Fellow-ship (grant no. 2016732). This work was supported by the Priestley JointPh.D. Scholarship from the University of Birmingham (UK) and The Uni-versity of Melbourne (Australia).Australia. National Health and Medical Research Council; 201673
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
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