Coarse-Grained Simulations of Release of Drugs Housed in Flexible Nanogels: New Insights into Kinetic Parameters

Funding: This research was funded by “Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, Programa Operativo FEDER Andalucía 2014-2020”, grant number P20_00138 as well as “Ministerio de Ciencia e Innovación”, grant numbers PID2020-116615RA-I00 and PGC2018-098770-B-I00.The diffusion-controlled release of drugs housed in flexible nanogels has been simulated with the help of a coarse-grained model that explicitly considers polymer chains. In these in silico experiments, the effect of its flexibility is assessed by comparing it with data obtained for a rigid nanogel with the same volume fraction and topology. Our results show that the initial distribution of the drug can exert a great influence on the release kinetics. This work also reveals that certain surface phenomena driven by steric interactions can lead to apparently counterintuitive behaviors. Such phenomena are not usually included in many theoretical treatments used for the analysis of experimental release kinetics. Therefore, one should be very careful in drawing conclusions from these formalisms. In fact, our results suggest that the interpretation of drug release curves in terms of kinetic exponents (obtained from the Ritger–Peppas Equation) is a tricky question. However, such curves can provide a first estimate of the drug diffusion coefficient.Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, Programa Operativo FEDER Andalucía 2014-2020, grant number P20_00138Ministerio de Ciencia e Innovación, grant numbers PID2020-116615RA-I00 and PGC2018-098770-B-I0

Low Back Pain in Cycling. Are There Differences between Road and Mountain Biking?

Low back pain (LBP) is known to affect cyclists. This study aimed to describe perceived lumbar dysfunction and compare the pain sensation in recreational cyclists who practice road and mountain biking. Forty males were randomly assigned to carry out a 3-h road cycling (RC) and mountain biking (MTB) time trial (TT) at submaximal intensity. LBP and pain pressure threshold (PPT) were measured before and after the TT. A significant increment at the LBP was found after RC TT (p 0.01). Low back pain perception increases with cycling in recreational cyclists. Nevertheless, this increase appears to be more related to the traits of the cyclist than the modality practiced

Condensation of Model Lipid Films by Cholesterol: Specific Ion Effects

The condensing effect and the ability of cholesterol (CHOL) to induce ordering in lipid films is a question of relevance in biological membranes such as the milk fat globule membrane (MFGM) in which the amount of CHOL influences the phase separation and mechanical resistance to rupture of coexisting phases relevant to emulsified food systems. Here, we study the effect of different salts (NaCl, CaCl2, MgCl2, LaCl3) on monolayers made of a model mixture of lipids (DPPC:DPPS 4:1) and CHOL. To this end, we apply Langmuir Film Balance to report a combined analysis of surface pressure-area (pi-A) and surface potential-area (DV–A) isotherms along with Micro-Brewster Angle Microscopy (Micro-BAM) images of the monolayers in the presence of the different electrolytes. We show that the condensation of lipid by CHOL depends strongly on the nature of the ions by altering the shape and features of the pi-A isotherms. DV–A isotherms provide further detail on the ion specific interactions with CHOL. Our results show that the condensation of lipids in the presence of CHOL depends on the combined action of ions and CHOL, which can alter the physical state of the monolayer.This research was funded by “Ministerio de Economía y Competitividad (MINECO), Plan Nacional de Investigación, Desarrollo e Innovación Tecnológica (I + D + i)”: Grant RYC-2012-10556, Projects MAT2015-63644-C2-1-R, RTI2018-101309-B-C21 and FIS2016-80087-C2-1-P, and European Regional Development Fund (ERDF). “Universidad de Granada” CEI-BIOTIC-BS14.2015. This study was also partially supported by “Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía”, ref. SOMM17/6105/UGR and SOMM17/6109/UGR

Quiebra

La continuación de la explotación de la empresa en quiebra por las cooperativas de trabajo se presenta como una oportunidad que no se debe desaprovechar dado que permite la conservación y administración del activo falencial, lo que resulta en mayores posibilidades de cobro del dividendo concursal por parte de los acreedores y la oportunidad de mantener las fuentes de trabajo para los trabajadores, lo que impacta directamente en la situación socioeconómica del país. En el presente trabajo abordaremos la continuación de la explotación de la empresa por los trabajadores nucleados en cooperativas de trabajo, luego de decretada la quiebra. Está orientado al análisis de la evolución de las mismas en el derecho concursal argentino y al estudio de la doctrina y leyes vinculadas con el tema.Fil: Brunetti Martín, Melisa. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Carello, Alberto Antonio. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Molina Arrué, Javier Andrés. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Venturi, Eliana Gabriela. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Fabrication of black-gold coatings by glancing angle deposition with sputtering

The fabrication of black-gold coatings using sputtering is reported here. Glancing angle deposition with a rotating substrate is needed to obtain vertical nanostructures. Enhanced light absorption is obtained in the samples prepared in the ballistic regime with high tilt angles. Under these conditions the diameter distribution of the nanostructures is centered at about 60 nm and the standard deviation is large enough to obtain black-metal behavior in the visible rangeEspaña Mineco MAT2014-59772-C2-1 MAT2015-69035-RED

Aggregation of liposomes induced by calcium : a structural and kinetic study

In this work, the calcium-induced aggregation of phosphatidylserine liposomes is probed by means of the analysis of the kinetics of such process as well as the aggregate morphology. This novel characterization of liposome aggregation involves the use of static and dynamic light-scattering techniques to obtain kinetic exponents and fractal dimensions. For salt concentrations larger than 5mM, a diffusion-limited aggregation regime is observed and the Brownian kernel properly describes the time evolution of the diffusion coefficient. For slow kinetics, a slightly modified multiple contact kernel is required. In any case, a time evolution model based on the numerical resolution of Smoluchowski's equation is proposed in order to establish a theoretical description for the aggregating system. Such a model provides an alternative procedure to determine the dimerization constant, which might supply valuable information about interaction mechanisms between phospholipid vesicles

Effect of the surface charge discretization on electric double layers. A Monte Carlo simulation study

The structure of the electric double layer in contact with discrete and continuously charged planar surfaces is studied within the framework of the primitive model through Monte Carlo simulations. Three different discretization models are considered together with the case of uniform distribution. The effect of discreteness is analyzed in terms of charge density profiles. For point surface groups,a complete equivalence with the situation of uniformly distributed charge is found if profiles are exclusively analyzed as a function of the distance to the charged surface. However, some differences are observed moving parallel to the surface. Significant discrepancies with approaches that do not account for discreteness are reported if charge sites of finite size placed on the surface are considered

Growth of lipid vesicle structures : from surface fractals to mass fractals

We study fractal vesicle aggregates whose morphology is conditioned by the interaction between the lipid vesicle membranes and calcium and magnesium ions. These morphologies are probed by means of static light scattering using a cross-correlation scheme that avoids the multiple intracluster scattering. In contrast to the branched structures induced by calcium, we report a singular surface- to mass-fractal transition controlled by the magnesium concentration. From infrared spectroscopy data we conclude that the specific dehydration of the lipid membranes due to these cations plays an essential role in short-range intervesicle interactions

Complexation of DNA with Thermoresponsive Charged Microgels: Role of Swelling State and Electrostatics

This research was funded by projects RTI2018-101309-B-C21 and PID2020-631-116615RA-I00, funded by MCIN/AEI/10.13039/501100011033 and by "ERDF A way of making Europe" and by project PY20_00138, funded by Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (PAIDI2020).Micro- and nanogels are being increasingly used to encapsulate bioactive compounds. Their soft structure allows large loading capacity while their stimuli responsiveness makes them extremely versatile. In this work, the complexation of DNA with thermoresponsive microgels is presented. To this end, PEGylated charged microgels based on poly-N-isopropylacrylamide have been synthesized, allowing one to explore the electrostatics of the complexation. Cationic microgels complexate spontaneously by electrostatic attraction to oppositely charged DNA as demonstrated by electrophoretic mobility of the complexes. Then, Langmuir monolayers reveal an increased interaction of DNA with swollen microgels (20 degrees C). Anionic microgels require the presence of multivalent cations (Ca2+) to promote the complexation, overcoming the electrostatic repulsion with negatively charged DNA. Then again, Langmuir monolayers evidence their complexation at the surface. However, the presence of Ca2+ seems to induce profound changes in the interaction and surface conformation of anionic microgels. These alterations are further explored by measuring adsorbed films with the pendant drop technique. Conformational changes induced by Ca2+ on the structure of the microgel can ultimately affect the complexation with DNA and should be considered in the design. The combination of microstructural and surface properties for microgels offers a new perspective into complexation of DNA with soft particles with biomedical applications.MCIN/AEI RTI2018-101309-B-C21 PID2020-631-116615RA-I00Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades PY20_0013

Specific ion effects on the electrokinetic properties of iron oxide nanoparticles: Experiments and simulations

We report experimental and simulation studies on ion specificity in aqueous colloidal suspensions of positively charged, bare magnetite nanoparticles. Magnetite has the largest saturation magnetization among iron oxides and relatively low toxicity, which explain why it has been used in multiple biomedical applications. Bare magnetite is hydrophilic and the sign of the surface charge can be changed by adjusting the pH, its isoelectric point being in the vicinity of pH = 7. Electrophoretic mobility of our nanoparticles in the presence of increasing concentrations of different anions showed that anions regarded as kosmotropic are more efficient in decreasing, and even reversing, the mobility of the particles. If the anions were ordered according to the extent to which they reduced the particle mobility, a classical Hofmeister series was obtained with the exception of thiocyanate, whose position was altered. Monte Carlo simulations were used to predict the diffuse potential of magnetite in the presence of the same anions. The simulations took into account the ion volume, and the electrostatic and dispersion forces among the ions and between the ions and the solid surface. Even though no fitting parameters were introduced and all input data were estimated using Lifshitz theory of van der Waals forces or obtained from the literature, the predicted diffusion potentials of different anions followed the same order as the mobility curves. The results suggest that ionic polarizabilities and ion sizes are to a great extent responsible for the specific ion effects on the electrokinetic potential of iron oxide particles.The authors thank the financial support from the following institutions: (i) ‘Ministerio de Economía y Competitividad, Plan Nacional de Investigación, Desarrollo e Innovación Tecnológica (I + D + i)’, Projects MAT2013-44429-R, MAT2012-36270-C04-04 and -02. (ii) ‘Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía’, Projects P09-FQM-4698, P10-FQM-5977, and P11-FQM-7074. (iii) European Regional Development Fund (ERDF)