Obtención y caracterización de nanopartículas poliméricas de ácido poli(láctico-co-glicólico)/ácido poli(gama-glutámico) conjugadas con ácido fólico para el transporte y liberación de doxorrubicina

Las nanopartículas poliméricas presentan una alternativa a la terapia convencional contra el cáncer, pues permiten aumentar la selectividad del tratamiento, minimizando los efectos secundarios no deseados en tejidos sanos. El PLGA y el γ-PGA, son polímeros utilizados en la obtención de nanopartículas para el transporte de fármacos. Los conjugados de ácido fólico (AF) pueden mejorar la entrega de fármacos a células tumorales por su interacción con receptores de folatos sobreexpresados en estos tejidos. Por ello, el objetivo de este estudio fue obtener y caracterizar un sistema de nanopartículas a base de PLGA y γ-PGA, funcionalizándolas con AF para el transporte y liberación de doxorrubicina (DOX), un agente antineoplásico. En este trabajo, se obtuvieron nanopartículas de PLGA mediante el método de emulsificación-evaporación del disolvente. La modificación superficial con γ-PGA presentó una señal a los 208 nm en UV-vis, mientras que la conjugación con AF mostró dos bandas a 280 nm y 348 nm. Cambios en las señales de FT-IR entre 1250 cm-1 y 1780 cm-1 indicaron las correctas modificaciones en las nanopartículas. Las imágenes de TEM/SEM mostraron estructuras cuasi-esféricas, con la presencia de cúmulos de material polimérico. Los tamaños de partícula (DLS) permanecieron menores a 600 nm y se observó cambio del potencial zeta de - 10.28 ± 1.37 mV a 14.2 ± 2.69 mV, después de las modificaciones realizadas. La eficiencia de encapsulado de doxorrubicina (DOX) fue de 47.97 ± 1.8 %, con una eficiencia de carga de 0.33 ± 0.012 %. El perfil de liberación de DOX-PLGA/γ-PGA-AF mostró responder a condiciones ácidas de pH (5.3), con un porcentaje de liberación de 55.42 ± 0.6 %. Finalmente, las nanopartículas DOX-PLGA/γ-PGA-AF fueron evaluadas en células HeLa, mostrando una disminución de la viabilidad celular de aproximadamente 60% a las 72 horas de exposición. La captación de las nanopartículas de PLGA/γ-PGA-AF mostró ser por endocitosis mediada por AF. Con base a los resultados obtenidos, se concluyó que las NPs de PLGA/γ-PGA-AF son un sistema potencial de transporte y entrega direccionada de fármacos, como la DOX, a través del reconocimiento molecular de receptores de folato sobreexpresados en algunos tipos de cáncer, haciéndolo un candidato adecuado para futuras aplicaciones terapéuticas.International Atomic Energy Agency (CRP-F22064, Contract No.18358

Biodegradable poly(D,L-lactide-co-glycolide)/poly(L-γ-glutamic acid) nanoparticles conjugated to folic acid for targeted delivery of doxorubicin

A novel targeted drug delivery nanoparticle system based on poly(D,L-lactide-co-glycolide) acid (PLGA) for delivery of doxorubicin (DOX) was developed. DOX-PLGA NPs were obtained by the emulsification-solvent evaporation technique. Then, their surface was modified with poly(L-γ-glutamic acid) (γ-PGA) and finally conjugated to modified folic acid (FA) as a targeting ligand. The surface modification and FA conjugation were followed by UV–Vis and FT-IR spectroscopies. Morphology was observed by TEM/SEM. Particle size, PDI and zeta potential were measured using DLS studies. Encapsulation and loading efficiencies, and DOX release kinetics were determined. Specific uptake and cell viability of DOX-PLGA/γ-PGA-FA NPs were tested in HeLa cells. Quasi-spherical nanoparticleswith a particle size lower than 600nm(DLS)were obtained. Spectroscopic techniques demonstrated the successful surface modification with γ-PGA and FA conjugation. Release profile of DOX-PLGA/γ-PGA-FA NPs showed a release of 55.4 ± 0.6% after seven days, in an acidic environment. HeLa cells exhibited a decrease in viability when treated with DOX-PLGA/γ-PGA-AF NPs, and cellular uptake was attributed to FA receptor-mediated endocytosis. These results suggest that DOX-PLGA/γ-PGA-FA NPs are a potential targeted drug carrier for further applications in cancer therapy.This study was supported by the International Atomic Energy Agency (CRP-F22064, Contract No. 18358) and the Universidad Autónoma del Estado de México, through the project No. 3543/2013CHT

177Lu-Bombesin-PLGA (paclitaxel): A targeted controlled-release nanomedicine for bimodal therapy of breast cancer

The gastrin-releasing peptide receptor (GRPr) is overexpressed in>75% of breast cancers. 177Lu-Bombesin (177Lu-BN) has demonstrated the ability to target GRPr and facilitate efficient delivery of therapeutic radiation doses to malignant cells. Poly(D,L‑lactide‑co‑glycolide) acid (PLGA) nanoparticles can work as smart drug controlled- release systems activated through pH changes. Considering that paclitaxel (PTX) is a first-line drug for cancer treatment, this work aimed to synthesize and chemically characterize a novel polymeric PTX-loaded nanosystem with grafted 177Lu-BN and to evaluate its performance as a targeted controlled-release nanomedicine for concomitant radiotherapy and chemotherapy of breast cancer. PLGA(PTX) nanoparticles were synthesized using the single emulsification-solvent evaporation method with PVA as a stabilizer in the presence of PTX. Thereafter, the activation of PLGA carboxylic groups for BN attachment through the Lys1-amine group was performed. Results of the chemical characterization by FT-IR, DLS, HPLC and SEM/TEM demonstrated the successful synthesis of BN-PLGA(PTX) with a hydrodynamic diameter of 163.54 ± 33.25 nm. The entrapment efficiency of paclitaxel was 92.8 ± 3.6%. The nanosystem showed an adequate controlled release of the anticancer drug, which increased significantly due to the pH change from neutral (pH=7.4) to acidic conditions (pH=5.3). After labeling with 177Lu and purification by ultrafiltration, 177Lu-BN-PLGA(PTX) was obtained with a radiochemical purity of 99 ± 1%. In vitro and in vivo studies using MDA-MB-231 breast cancer cells (GRPr-positive) demonstrated a 177Lu-BNPLGA( PTX) specific uptake and a significantly higher cytotoxic effect for the radiolabeled nanosystem than the unlabeled BN-PLGA(PTX) nanoparticles. Using a pulmonary micrometastasis MDA-MB-231 model, the added value of 177Lu-BN-PLGA(PTX) for tumor imaging was confirmed. The 177Lu-BN-PLGA(PTX) nanomedicine is suitable as a targeted paclitaxel delivery system with concomitant radiotherapeutic effect for the treatment of GRPr-positive breast cancer.This study was partially supported by the National Council of Science and Technology (CONACyT-CB-A1S38087) and the International Atomic Energy Agency (CRP-F22064, Contract 18358). It was carried out as part of the activities of the “Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos, CONACyT

A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period.

AIM:We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. MATERIAL AND METHODS:In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. RESULTS:In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). CONCLUSION:The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance

ENGIU: Encuentro Nacional de Grupos de Investigación de UNIMINUTO.

El desarrollo del prototipo para el sistema de detección de Mina Antipersona (MAP), inicia desde el semillero ADSSOF perteneciente al programa de Administración en Seguridad y Salud en el trabajo de la UNIMINUTO, se realiza a partir de un detector de metales que emite una señal audible, que el usuario puede interpretar como aviso de presencia de un objeto metálico, en este caso una MAP. La señal audible se interpreta como un dato, como ese dato no es perceptible a 5 metros de distancia, se implementa el transmisor de Frecuencia Modulada FM por la facilidad de modulación y la escogencia de frecuencia de transmisión de acuerdo con las normas y resolución del Ministerio de Comunicaciones; de manera que esta sea la plataforma base para enviar los datos obtenidos a una frecuencia establecida. La idea es que el ser humano no explore zonas peligrosas y buscar la forma de crear un sistema que permita eliminar ese riesgo, por otro lado, buscar la facilidad de uso de elementos ya disponibles en el mercado