Examinando por Autor "Velásquez, Luis"
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Ítem Development of a PHBV nanoparticle as a peptide vehicle for NOD1 activation(Taylor and Francis Ltd., 2021) Cabaña-Brunod, Mauricio; Herrera, Pablo A.; Márquez-Miranda, Valeria; Llancalahuen, Felipe M.; Duarte, Yorley; González-Nilo, Danilo; Fuentes, Juan A.; Vilos, Cristián; Velásquez, Luis; Otero, CarolinaNOD1 is an intracellular receptor that, when activated, induces gene expression of pro-inflammatory factors promoting macrophages and neutrophils recruitment at the infection site. However, iE-DAP, the dipeptide agonist that promotes this receptor's activation, cannot permeate cell membranes. To develop a nanocarrier capable of achieving a high and prolonged activation over time, iE-DAP was encapsulated in nanoparticles (NPs) made of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The physicochemical properties, colloidal stability, encapsulation efficiency, and cellular uptake of iE-DAP-loaded PHVB NPs were analyzed. Results evidenced that physicochemical properties of iE-DAP-loaded NPs remained stable over time, and NPs were efficiently internalized into cells, a process that depends on time and concentration. Moreover, our results showed that NPs elicited a controlled cargo release in vitro, and the encapsulated agonist response was higher than its free form, suggesting the possibility of activating intracellular receptors triggering an immune response through the release of NOD1 agonist.Ítem Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake(SPRINGER, 2016-02) Márquez-Miranda, Valeria; Peñaloza, Juan Pablo; Araya-Durán, Ingrid; Reyes, Rodrigo; Vidaurre, Soledad; Romero, Valentina; Fuentes, Juan; Céric, Francisco; Velásquez, Luis; González-Nilo, Fernando D.; Otero, CarolinaPoly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes.Ítem La Heterogeneidad del Alfabetismo en Salud y el Consentimiento Informado en Chile(Sociedad Chilena de Psicología Clínica, 2012-12) Saavedra-Dahm, Oscar; Solar, Paula; Díaz, Hernán; Mandel, Astrid; Casado, María; Orihuela, Pedro; Rivera, María; Velásquez, Luis; Cardenas, HugoSe examinó el alfabetismo en salud en Chile con el fin de determinar si se pueden usar procedimientos de consentimiento informado estándares en esta población. Se evaluó el alfabetismo en salud con la versión abreviada de la prueba SAHLSA. Los resultados se expresaron como el porcentaje de respuestas correctas en cada prueba. El promedio global de respuestas correctas fue 85.4 ± 13.5 % (media aritmética ± desviación estándar, n=762). Hubo diferencias importantes entre los subgrupos examinados. El nivel más bajo de alfabetismo en salud se detectó en pescadores artesanales y sus familias y en estudiantes de liceos públicos, y el más alto en estudiantes universitarios y madres pobladoras atendidas en el sistema público de salud. Los resultados muestran la necesidad que los procedimientos de consentimiento informado tomen en cuenta la heterogeneidad del alfabetismo en salud de la población chilena.Ítem Multifunctional polymeric nanoparticles doubly loaded with SPION and ceftiofur retain their physical and biological properties(BioMed Central Ltd., 2015-02) Solar, Paula; González, Guillermo; Vilos, Cristian; Herrera, Natalia; Juica, Natalia; Moreno, Mabel; Simon, Felipe; Velásquez, LuisBackground: Advances in nanostructure materials are leading to novel strategies for drug delivery and targeting, contrast media for magnetic resonance imaging (MRI), agents for hyperthermia and nanocarriers. Superparamagnetic iron oxide nanoparticles (SPIONs) are useful for all of these applications, and in drug-release systems, SPIONs allow for the localization, direction and concentration of drugs, providing a broad range of therapeutic applications. In this work, we developed and characterized polymeric nanoparticles based on poly (3-hydroxybutyric acid-co-hydroxyvaleric acid) (PHBV) functionalized with SPIONs and/or the antibiotic ceftiofur. These nanoparticles can be used in multiple biomedical applications, and the hybrid SPION-ceftiofur nanoparticles (PHBV/SPION/CEF) can serve as a multifunctional platform for the diagnosis and treatment of cancer and its associated bacterial infections. Results: Morphological examination using transmission electron microscopy (TEM) showed nanoparticles with a spherical shape and a core-shell structure. The particle size was evaluated using dynamic light scattering (DLS), which revealed a diameter of 243.0 ± 17 nm. The efficiency of encapsulation (45.5 ± 0.6% w/v) of these polymeric nanoparticles was high, and their components were evaluated using spectroscopy. UV-VIS, FTIR and DSC showed that all of the nanoparticles contained the desired components, and these compounds interacted to form a nanocomposite. Using the agar diffusion method and live/dead bacterial viability assays, we demonstrated that these nanoparticles have antimicrobial properties against Escherichia coli, and they retain their magnetic properties as measured using a vibrating sample magnetometer (VSM). Cytotoxicity was assessed in HepG2 cells using live/dead viability assays and MTS, and these assays showed low cytotoxicity with IC50 > 10 mg/mL nanoparticles. Conclusions: Our results indicate that hybrid and multifunctional PHBV/SPION/CEF nanoparticles are suitable as a superparamagnetic drug delivery system that can guide, concentrate and site-specifically release drugs with antibacterial activity. © 2015 Solar et al.