Evaluación de la cinética de liberación de compuestos hidrofílicos y lipofílicos a partir de nanopartículas híbridas polímero-lípido

Evaluation of the release kinetics of hydrophilic and lipophilic compounds from polymer-lipid hybrid nanoparticles

Juan Pablo Carmona Almazán (2023, [Tesis de maestría])

En el tratamiento de enfermedades, la administración de dosis múltiples es una estrategia común para mantener la concentración de los fármacos dentro de un margen terapéutico. Sin embargo, la adherencia de los pacientes a este tipo de tratamiento puede ser un desafío, llevando a una administración irregular de dosis. Una alternativa utilizada para abordar este reto son las nanopartículas híbridas polímero/lípido(NPPLs), las cuales, con menos administraciones, tienen el potencial de alcanzar la dosis necesaria en el tratamiento, posibilitando entonces el incremento del apego al tratamiento. En nuestro proyecto, se llevó a cabo la síntesis de nanopartículas de ácido poli láctico-co-glicólico (PLGA) recubiertas de lecitina de soya, por medio de técnicas de nanoprecipitación y autoensamblaje. Además, integramos estas nanopartículas en una matriz polimérica a base de aerogeles de gelatina de manera que estuvieran distribuidas de manera homogénea y concentrada. Nuestro enfoque central radica en entender la cinética de liberación de un compuesto hidrofílico (ácido gálico) y uno lipofílico (quercetina) a partir de este sistema. Logramos sintetizar nanopartículas con un diámetro hidrodinámico de 100 ± 15 nm, 153 ± 33 y149±21 nm, en el caso de las nanopartículas vacías y cargadas con ácido gálico y cargadas con quercetina, respectivamente. La eficiencia de encapsulación del ácido gálico fue del 90 ± 5 % y de la quercetina fue del 70 ± 10 %. Los resultados que obtuvimos muestran que el ácido gálico sigue una cinética del modelo de Korsmeyer-Peppas, con un valor de n = 1.01 y la quercetina una cinética de primer orden. Dado que los compuestos encapsulados tuvieron una liberación más lenta con respecto a los compuestos libres en los aerogeles de gelatina, nuestro trabajo indica que el encapsulamiento en NPPLs de un compuesto bioactivo, independientemente de su naturaleza química, puede ayudar a retrasar su liberación y reducir el número de dosis administradas, en consecuencia, esto pudiera contribuir a incrementar el apego de un paciente al tratamiento.

In the treatment of diseases, the administration of multiple doses is a common strategy to maintain drug concentrations within a therapeutic range. However, patient adherence to this type of treatment can be challenging, resulting in irregular dosing. An alternative approach used to address this challenge involves polymer/lipid hybrid nanoparticles (NPPLs), which have the potential to achieve the necessary drug dose with fewer administrations, thereby increasing treatment adherence. In our project, we synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with soy lecithin using nanoprecipitation and self-assembly techniques. These nanoparticles were then integrated into a polymer matrix based on gelatin aerogels to ensure homogeneous and concentrated distribution. Our main focus was to understand the release kinetics of a hydrophilic compound (gallic acid) and a lipophilic one (quercetin) from this system. We successfully synthesized nanoparticles with a hydrodynamic diameter of 100 ± 15 nm, 153 ± 33 nm, and 149 ± 21 nm for empty nanoparticles, gallic acid-loaded, and quercetin-loaded nanoparticles, respectively. The encapsulation efficiency was 90 ± 5 % for gallic acid and 70 ± 10 % for quercetin. The results we obtained indicate that gallic acid follows Korsmeyer-Peppas kinetics with a value of n = 1.01, while quercetin exhibits first-order kinetics. Since the encapsulated compounds showed slower release compared to free compounds in gelatin aerogels, our work suggests that encapsulation in NPPLs with a bioactive compound, regardless of its chemical nature, can help delay its release and reduce the number of doses administered. Consequently, this could contribute to improve patient treatment adherence.

nanopartículas híbridas, cinética de liberación, sistemas poliméricos, PLGA/lecitina, compuestos hidrofílicos y lipofílicos hybrid nanoparticles, release kinetics, polymeric systems, PLGA/lecithin, hydrophilic and lipophilic compounds INGENIERÍA Y TECNOLOGÍA CIENCIAS TECNOLÓGICAS INGENIERÍA Y TECNOLOGÍA QUÍMICAS ANÁLISIS DE POLÍMEROS ANÁLISIS DE POLÍMEROS

Effects of geostrophic kinetic energy on the distribution of mesopelagic fish larvae in the southern Gulf of California in summer/fall stratified seasons

FERNANDO CONTRERAS CATALA (2016, [Artículo])

Effects of geostrophic kinetic energy flux on the three-dimensional distribution of fish larvae of mesopelagic species (Vinciguerria lucetia, Diogenichthys laternatus, Benthosema panamense and Triphoturus mexicanus) in the southern Gulf of California during summer and fall seasons of stronger stratification were analyzed. The greatest larval abundance was found at sampling stations in geostrophic kinetic energy-poor areas (<7.5 J/m3), where the distribution of the dominant species tended to be stratified. Larvae of V. lucetia (average abundance of 318 larvae/10m2) and B. panamense (174 larvae/10m2) were mostly located in and above the pycnocline (typically ∼ 40 m depth). In contrast, larvae of D. laternatus (60 larvae/10m2) were mainly located in and below the pycnocline. On the other hand, in sampling stations from geostrophic kinetic energy-rich areas (> 21 J/m3), where mesoscale eddies were present, the larvae of the dominant species had low abundance and were spread more evenly through the water column, in spite of the water column stratification. For example, in a cyclonic eddy, V. lucetia larvae (34 larvae/10m2) extended their distribution to, at least, the limit of sampling 200 m depth below the pycnocline, while D. laternatus larvae (29 larvae/10m2) were found right up to the surface, both probably as a consequence mixing and secondary circulation in the eddy. Results showed that the level of the geostrophic kinetic energy flux affects the abundance and the three-dimensional distribution of mesopelagic fish larvae during the seasons of stronger stratification, indicating that areas with low geostrophic kinetic energy may be advantageous for feeding and development of mesopelagic fish larvae because of greater water column stability. © 2016 Contreras-Catala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Article, autumn, Benthosema panamense, Diogenichthys laternatus, environmental factor, environmental parameters, fish, geographic distribution, geostrophic kinetic energy, hydrography, larva, nonhuman, population abundance, population dispersion, pop CIENCIAS FÍSICO MATEMÁTICAS Y CIENCIAS DE LA TIERRA CIENCIAS DE LA TIERRA Y DEL ESPACIO OCEANOGRAFÍA OCEANOGRAFÍA

Octopus maya white body show sex-specific transcriptomic profiles during the reproductive phase, with high differentiation in signaling pathways

Oscar Juárez (2019, [Artículo])

White bodies (WB), multilobulated soft tissue that wraps the optic tracts and optic lobes, have been considered the hematopoietic organ of the cephalopods. Its glandular appearance and its lobular morphology suggest that different parts of the WB may perform different functions, but a detailed functional analysis of the octopus WB is lacking. The aim of this study is to describe the transcriptomic profile of WB to better understand its functions, with emphasis on the difference between sexes during reproductive events. Then, validation via qPCR was performed using different tissues to find out tissue-specific transcripts. High differentiation in signaling pathways was observed in the comparison of female and male transcriptomic profiles. For instance, the expression of genes involved in the androgen receptor-signaling pathway were detected only in males, whereas estrogen receptor showed higher expression in females. Highly expressed genes in males enriched oxidation-reduction and apoptotic processes, which are related to the immune response. On the other hand, expression of genes involved in replicative senescence and the response to cortisol were only detected in females. Moreover, the transcripts with higher expression in females enriched a wide variety of signaling pathways mediated by molecules like neuropeptides, integrins, MAPKs and receptors like TNF and Toll-like. In addition, these putative neuropeptide transcripts, showed higher expression in females’ WB and were not detected in other analyzed tissues. These results suggest that the differentiation in signaling pathways in white bodies of O. maya influences the physiological dimorphism between females and males during the reproductive phase. © 2019 Juárez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

androgen receptor, integrin, mitogen activated protein kinase, neuropeptide, transcriptome, tumor necrosis factor, argonaute protein, corticotropin releasing factor receptor, corticotropin releasing factor receptor 2, DEAD box protein, estradiol 17be BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOLOGÍA ANIMAL (ZOOLOGÍA) BIOLOGÍA ANIMAL (ZOOLOGÍA)

A simple extension to the CMASA method for the prediction of catalytic residues in the presence of single point mutations

David Israel Flores Granados (2014, [Artículo])

The automatic identification of catalytic residues still remains an important challenge in structural bioinformatics. Sequence-based methods are good alternatives when the query shares a high percentage of identity with a well-annotated enzyme. However, when the homology is not apparent, which occurs with many structures from the structural genome initiative, structural information should be exploited. A local structural comparison is preferred to a global structural comparison when predicting functional residues. CMASA is a recently proposed method for predicting catalytic residues based on a local structure comparison. The method achieves high accuracy and a high value for the Matthews correlation coefficient. However, point substitutions or a lack of relevant data strongly affect the performance of the method. In the present study, we propose a simple extension to the CMASA method to overcome this difficulty. Extensive computational experiments are shown as proof of concept instances, as well as for a few real cases. The results show that the extension performs well when the catalytic site contains mutated residues or when some residues are missing. The proposed modification could correctly predict the catalytic residues of a mutant thymidylate synthase, 1EVF. It also successfully predicted the catalytic residues for 3HRC despite the lack of information for a relevant side chain atom in the PDB file. © 2014 Flores et al.

1UU9 protein, 3HRC protein, protein, thymidylate synthase, unclassified drug, protein kinase, thymidylate synthase, accuracy, algorithm, Article, CMASA, CMASA Substitution Matrix, Contact Matrix Average Deviation, controlled study, correlation coeffi CIENCIAS FÍSICO MATEMÁTICAS Y CIENCIAS DE LA TIERRA MATEMÁTICAS ANÁLISIS NUMÉRICO ANÁLISIS NUMÉRICO

Enhancement of antibiotics antimicrobial activity due to the silver nanoparticles impact on the cell membrane

Roberto Vazquez-Munoz (2019, [Artículo])

The ability of microorganisms to generate resistance outcompetes with the generation of new and efficient antibiotics; therefore, it is critical to develop novel antibiotic agents and treatments to control bacterial infections. An alternative to this worldwide problem is the use of nanomaterials with antimicrobial properties. Silver nanoparticles (AgNPs) have been extensively studied due to their antimicrobial effect in different organisms. In this work, the synergistic antimicrobial effect of AgNPs and conventional antibiotics was assessed in Gram-positive and Gram-negative bacteria. AgNPs minimal inhibitory concentration was 10–12 μg mL-1 in all bacterial strains tested, regardless of their different susceptibility against antibiotics. Interestingly, a synergistic antimicrobial effect was observed when combining AgNPs and kanamycin according to the fractional inhibitory concentration index, FICI: <0.5), an additive effect by combining AgNPs and chloramphenicol (FICI: 0.5 to 1), whereas no effect was found with AgNPs and β-lactam antibiotics combinations. Flow cytometry and TEM analysis showed that sublethal concentrations of AgNPs (6–7 μg mL-1) altered the bacterial membrane potential and caused ultrastructural damage, increasing the cell membrane permeability. No chemical interactions between AgNPs and antibiotics were detected. We propose an experimental supported mechanism of action by which combinatorial effect of antimicrobials drives synergy depending on their specific target, facilitated by membrane alterations generated by AgNPs. Our results provide a deeper understanding about the synergistic mechanism of AgNPs and antibiotics, aiming to combat antimicrobial infections efficiently, especially those by multi-drug resistant microorganisms, in order to mitigate the current crisis due to antibiotic resistance. © 2019 Vazquez-Muñoz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ampicillin, antibiotic agent, aztreonam, beta lactam antibiotic, biapenem, chloramphenicol, kanamycin, silver nanoparticle, silver nitrate, antiinfective agent, metal nanoparticle, silver, antibiotic sensitivity, antimicrobial activity, Article, bact BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOFÍSICA BIOFÍSICA

Phylogenetic relationships of Pseudo-nitzschia subpacifica (Bacillariophyceae) from the Mexican Pacific, and its production of domoic acid in culture

Sonia Quijano (2020, [Artículo])

Pseudo-nitzschia is a cosmopolitan genus, some species of which can produce domoic acid (DA), a neurotoxin responsible for the Amnesic Shellfish Poisoning (ASP). In this study, we identified P. subpacifica for the first time in Todos Santos Bay and Manzanillo Bay, in the Mexican Pacific using SEM and molecular methods. Isolates from Todos Santos Bay were cultivated under conditions of phosphate sufficiency and deficiency at 16°C and 22°C to evaluate the production of DA. This toxin was detected in the particulate (DAp) and dissolved (DAd) fractions of the cultures during the exponential and stationary phases of growth of the cultures. The highest DA concentration was detected during the exponential phase grown in cells maintained in P-deficient medium at 16°C (1.14 ± 0.08 ng mL-1 DAd and 4.71 ± 1.11 × 10−5 ng cell-1 of DAp). In P-sufficient cultures DA was higher in cells maintained at 16°C (0.25 ± 0.05 ng mL-1 DAd and 9.41 ± 1.23 × 10−7 ng cell-1 of DAp) than in cells cultured at 22°C. Therefore, we confirm that P. subpacifica can produce DA, especially under P-limited conditions that could be associated with extraordinary oceanographic events such as the 2013–2016 "Blob" in the northeastern Pacific Ocean. This event altered local oceanographic conditions and possibly generated the presence of potential harmful species in areas with economic importance on the Mexican Pacific coast. © 2020 Quijano-Scheggia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

domoic acid, domoic acid, kainic acid, Article, cell growth, controlled study, diatom, Mexico, morphology, nonhuman, Pacific Ocean, phylogeny, plant cell, plant growth, Pseudo nitzschia, toxin analysis, cell culture technique, classification, diatom, CIENCIAS FÍSICO MATEMÁTICAS Y CIENCIAS DE LA TIERRA CIENCIAS DE LA TIERRA Y DEL ESPACIO OCEANOGRAFÍA OCEANOGRAFÍA