Nanopartículas Poliméricas en Dermocosmética

Indexación: Web of Science; Scielo.Recent advances in the fields of biomaterials and nanotechnology have allowed the development of advanced nanoparticles for biomedical applications. Despite a vast number of nanostructures such as liposomes, solid­lipid nanocapsules, polymeric and hybrid lipid­polymer nanoparticles have been studied as carriers for drug delivery for different pathologies with remarkable promising results; the use of polymeric nanoparticles in dermocosmetic still has not been widely explored. The evolution of cosmetic into the care skin and dermatology represents novel technological challenges. Also, the increasing knowledge about normal skin physiology and advances in nanotechnology provide an attractive environment for the creation of innovative dermocosmetic formulations. In this work, we discuss the state of the art of polymeric nanoparticles formulated for dermocosmetics, its mechanisms of action, and diffusion into the skin.Los recientes avances en el campo de los biomateriales y la nanotecnología han permitido el desarrollo de nanopartículas avanzadas para aplicaciones biomédicas. A pesar de que un gran número de nanoestructuras tales como liposomas, nanocápsulas lípido-sólidas, nanopartículas poliméricas y lípido-polímero híbridas han sido estudiadas como vehículos para la administración de fármacos en diferentes patologías con notables resultados prometedores, el uso de nanopartículas poliméricas en dermocosmética todavía no ha sido ampliamente explorado. La evolución de la cosmética en el cuidado de la piel y la dermatología nos enfrentan a nuevos retos tecnológicos. Además, el aumento de los conocimientos sobre la fisiología de la piel normal y los avances en la nanotecnología proporcionan un entorno atractivo para la creación de formulaciones dermocosméticas innovadoras. En este trabajo se discute el estado del arte de las nanopartículas poliméricas desarrolladas para dermocosmética, sus mecanismos de acción y la difusión en la piel.http://ref.scielo.org/b68hz

Superparamagnetic Poly (3-hydroxybutyrate-co-3 hydroxyvalerate) (PHBV) nanoparticles for biomedical applications

Indexación: ScieloBackground: The progress in material science and the recent advances in biodegradable/biocompatible polymers and magnetic iron oxide nanoparticles have led to develop innovative diagnostic and therapeutic strategies for diseases based on multifunctional nanoparticles, which include contrast medium for magnetic resonance imaging, agent for hyperthermia and nanocarriers for targeted drug delivery. The aim of this work is to synthesize and characterize superparamagnetic iron oxide (magnetite), and to encapsulate them into poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles for biomedical applications. Results: The magnetite nanoparticles were confirmed by X-ray diffraction and exhibited a size of 22.3 ± 8.8 nm measured by transmission electron microscopy (TEM). Polymeric PHBV nanoparticles loaded with magnetite (MgNPs) were analyzed using dynamic light scattering and showed a size of 258.6 ± 35.7 nm and a negative zeta potential (-10.8 ± 3.5 mV). The TEM examination of MgNPs exhibited a spherical core-shell structure and the magnetic measurements showed in both, non-encapsulated magnetite and MgNPs, a superparamagnetic performance. Finally, the in vitro studies about the magnetic retention of MgNPs in a segment of small intestine of rats showed an active accumulation in the region of the magnetic field. Conclusions: The results obtained make the MgNPs suitable as potential magnetic resonance imaging contrast agents, also promoting hyperthermia and even as potential nanocarriers for site-specific transport and delivery of drugs. Keywords: hyperthermia, magnetic resonance image (MRI), magnetite, PHBV, polymeric nanoparticles.http://ref.scielo.org/cxt57

Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

<p>Abstract</p> <p>Background</p> <p>The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation.</p> <p>Methods</p> <p>Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL). For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features.</p> <p>Results</p> <p>We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation.</p> <p>Conclusions</p> <p>Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible new transcription factors orchestrating the CERTL opens new alternatives for understanding gene expression regulation in uterine function.</p

Revisión bibliográfica: hemocompatibilidad de nanopartículas poliméricas como transportadores de fármacos

67 p.Debido al desarrollo de la nanomedicina en la actualidad, se han logrado implementar mejoras tanto en técnicas de diagnóstico como terapéuticas, permitiendo mejorar la eficacia de los tratamientos al ser dirigidos, logrando que la terapia convencional sea más exitosa. Esta revisión se realizó para tener un mejor entendimiento de la hemocompatibilidad de las nanopartículas (NPs) poliméricas como transportadores de fármacos, mediante los procesos fisiológicos que desencadenan en la circulación sanguínea. Para esto es necesario saber las características de síntesis de las NPs poliméricas como; nanomateriales utilizados, caracterización de las NPs, farmacocinética del fármaco transportado, ya que esto mediará su comportamiento ante los componentes sanguíneos, generando; hemólisis, activación del sistema inmune, agregación plaquetaria y activación de la cascada de coagulación, activación del complemento y/o agregación de proteínas plasmáticas presentes en el plasma, por donde se desplazarán las NPs poliméricas hasta llegar al sitio de acción del fármaco. Las interacciones que realicen las NPs con la sangre va a depender de su caracterización; tamaño, carga superficial y forma, ya que cada proceso de síntesis diferencia unas NPs de otras, independiente si el nanomaterial utilizado es el mismo, cada formulación será única por los ligandos incorporados en su superficie. Aún falta una mayor preocupación para conocer la hemocompatibilidad de las NPs como transportadores de fármacos por parte de los proyectos que las desarrollan, y no solo evaluar la toxicidad del fármaco en la sangre, sino también del nanomaterial utilizado para encapsularlo, el cual estará en contacto con el sistema al que se le administrará, con el fin de evitar el desarrollo de patologías adicionales a las presentadas

Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors

Indexación: Scopus.Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.https://www.nature.com/articles/s41598-017-14040-5.pd

Citotoxidad de 10 derivados de labdanos, de potencial actividad anti-ulcerogenica

76 p.En esta investigación se probó la citotoxicidad de diez compuestos sintetizados en un trabajo previo, mediante adición de distintos radicales a dos diterpenos de tipo labdano, aislados de la resina de Araucaria araucana: ácido 15 acetiloxiimbricatólico (Rf-1) y ácido 15-hidroxiimbricatólico (Rf-2). La citotoxicidad se determinó por medio de pruebas sobre viabilidad de cultivos de fibroblastos MRC-5 y células neoplásicas AGS, entre las que se cuentan reducción de la sal de tetrazolio e incorporación de rojo neutro. La citotoxicidad se expresó en función de los valores IC50 de cada compuesto. Los valores obtenidos muestran que los compuestos Rf 3, 6, 7, 8, 9 y 12 no presentan citotoxicidad basal, a valores de hasta 1000 µM, sobre las líneas celulares sometidas a estudio. Los resultados muestran claramente que los compuestos Rf-10 y Rf-13 presentan toxicidad basal, a valores menores de 1000 µM, tanto en la línea celular AGS como en los fibroblastos MRC-5. Por otra parte, los compuestos Rf-4 y Rf-5 presentan mayor citotoxicidad basal que los otros compuestos, sobre la línea celular tumoral, pero no sobre fibroblastos, evidenciando su potencial como agentes antitumorales. Esto permite, en el futuro, enfocar los estudios hacia esta área. Los resultados son significativamente promisorios y permiten continuar analizando su efectividad como agentes gastroprotectores y antitumorales

Ceftiofur-loaded PHBV microparticles: A potential formulation for a long-acting antibiotic to treat animal infections

Background: The infectious diseases in the livestock breeding industry represent a significant drawback that generates substantial economic loss and have led to the indiscriminate use of antibiotics. The formulation of polymeric microparticles loaded with antibiotics for veterinary use can: reduce the number of required doses; protect the drug from inactivation; and maintain a sustained-release of the antibiotic drug at effective levels. Accomplishing all of these goals would have a significant economic and animal health impact on the livestock breeding industry. Results: In this work, we formulated ceftiofur-loaded PHBV microparticles (PHBV-CEF) with a spherical shape, a smooth surface and diameter sizes between 1.65 and 2.37 \u3bcm. The encapsulation efficiency was 39.5 \ub1 1.1% w/w, and we obtained a sustained release of ceftiofur in PBS-buffer (pH 7.4) over 7 days. The antibacterial activity of ceftiofur was preserved after the encapsulation procedure, and toxicity of PHBV-CEF microparticles evaluated by MTS was represented by an IC50 &gt; 10 mg/mL. Conclusions: Our results suggest that PHBV-CEF particles have a potential application for improving the treatment of infectious diseases in the livestock breeding industry

Superparamagnetic Poly (3-hydroxybutyrate-co-3 hydroxyvalerate) (PHBV) nanoparticles for biomedical applications

Background: The progress in material science and the recent advances in biodegradable/biocompatible polymers and magnetic iron oxide nanoparticles have led to develop innovative diagnostic and therapeutic strategies for diseases based on multifunctional nanoparticles, which include contrast medium for magnetic resonance imaging, agent for hyperthermia and nanocarriers for targeted drug delivery. The aim of this work is to synthesize and characterize superparamagnetic iron oxide (magnetite), and to encapsulate them into poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles for biomedical applications. Results: The magnetite nanoparticles were confirmed by X-ray diffraction and exhibited a size of 22.3 \ub1 8.8 nm measured by transmission electron microscopy (TEM). Polymeric PHBV nanoparticles loaded with magnetite (MgNPs) were analyzed using dynamic light scattering and showed a size of 258.6 \ub1 35.7 nm and a negative zeta potential (-10.8 \ub1 3.5 mV). The TEM examination of MgNPs exhibited a spherical core-shell structure and the magnetic measurements showed in both, non-encapsulated magnetite and MgNPs, a superparamagnetic performance. Finally, the in vitro studies about the magnetic retention of MgNPs in a segment of small intestine of rats showed an active accumulation in the region of the magnetic field. Conclusions: The results obtained make the MgNPs suitable as potential magnetic resonance imaging contrast agents, also promoting hyperthermia and even as potential nanocarriers for site-specific transport and delivery of drugs

PCSK9 conjugated liposomes for targeted delivery of paclitaxel to the cancer cell: A proof-of-concept study.

Ligand-based targeting of the receptors that are overexpressed explicitly on cancer cells represents an effective drug delivery approach to enhance the chemotherapeutic efficacy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) which is a serine protease enzyme primarily produced by the liver cells, can potentially be used as a targeting ligand. PCSK9 binds to the LDL-r on hepatocytes' surface, leading to endocytosis and endosomal degradation. High LDL-r expression, which is believed to meet the higher demand of the cholesterol and phospholipids to build proliferating cancer cell membrane, ensures selective uptake of the PCSK9 conjugated liposomes. In the present work, the PCSK9 conjugated liposomal system was developed to deliver paclitaxel (PTX) to cancer cells. The protein was conjugated by EDC and NHS in a two-step coupling reaction to the liposomes containing COOH-PEG-COOH lipid. Conjugation was confirmed by NMR, and liposomes were further characterized by SEM and zeta sizer. PCSK9-conjugated liposomes showed high encapsulation efficiency of 69.1% with a diameter of 90.0 ± 4.9 nm. Long-term stability (30 days) study (Zeta potential: -9.88) confirmed excellent constancy and significant drug retention (58.2%). Invitro cytotoxicity and targeting efficiency was explored using MTS assay in human embryonic kidney cells (HEK293), liver hepatocellular cells (HEPG2), and a human colon cancer cell line (HCT116) for 24 h. PCSK9 conjugated liposomes exhibited significantly higher growth inhibition than the unconjugated (control) liposomes in HCT116 cell line (p < 0.001). The novel PCSK9 conjugated liposomes presented potent and precise in vitro anticancer activity and, therefore, are suggested for the first time as a promising targeted delivery system for cancer treatment

Nanotransportadores de agentes terapéuticos para tratamiento de cáncer colorrectal: diseño racional de nanopartículas para la encapsulación, transporte y liberación de fármacos

55 p.El cáncer colorrectal (CCR), se ubica como el segundo tipo de cáncer más frecuente en mujeres y el tercero en hombres. Actualmente, el tratamiento de esta afección se enfoca en el uso de gentes citotóxicos que inhiben la proliferación de células cancerígenas; sin embargo, su acción también afecta a las células sanas debido a su baja especificidad. En los últimos años, se han descrito diversos tratamientos basados en sistemas de administración de fármacos mediante nanopartículas poliméricas, debido a su alta biocompatibilidad, su adecuada utilidad para la encapsulación de fármacos tanto hidrófobos como hidrofílicos y debido a que se encuentran aprobado por la Food and Drug Administration (FDA). Por otra parte, se ha descrito que la adición de polietilenglicol (PEG) otorga una mejora en la capacidad de transporte de fármacos. A la fecha, no existe amplia evidencia científica que estudie los procesos de liberación de agentes quimioterapéuticos, considerando características conformacionales y químicas de nanotransportadores poliméricos, desde el punto de vista de la química computacional. En el presente proyecto estudiamos mediante técnicas avanzadas de dinámica molecular, modelado computacional y cálculos de fuerza, los factores que afectan el proceso de liberación de fármacos a través de sistemas nanopoliméricos PLA/PLGA: DSPE-PEG2000 conjugados con terminales COO-, NH2 y OCH3. Logrando así, comprender que la naturaleza del núcleo de las nanosuperficies jugaría un papel fundamental en la liberación de los fármacos de estudio, donde en nanopartículas con centro basado en PLGA se presentaría una mayor afinidad por las drogas en comparación a sistemas con núcleo basado en PLA. Por otra parte, se encontraron indicios de que la agregación de terminales NH2 y OCH3 generarían sistemas más compactos en comparación a los que presentan COO-, lo que podría incidir en la cinética de liberación. El entendimiento de los factores estructurales y energéticos que dominan la interacción y liberación de fármacos anticancerígenos desde nanotransportadores, proporciona información que permite mejorar el diseño racional de nanopartículas poliméricas inteligentes en el transporte y liberación de fármacos contra el cáncer colorrectal. // ABSTRACT: Colorectal cancer (CRC) is the second most frequent type of cancer in women and the third in men. Currently, the treatment of this condition is focused on the use of cytotoxic agents that inhibit the proliferation of cancer cells. However, at the same time, they induce cell death in healthy tissue due to their lack of specificity. In recent years, several treatments based on drug delivery systems using polymeric nanoparticles have been described, due to their high biocompatibility, their usefulness for the encapsulation of hydrophobic and hydrophilic drugs, and because they are approved by the Food and Drug Administration (FDA). On the other hand, it has been described that the addition of polyethylene glicol (PEG) improves drug transport capacity. To date, not many works analyze the reléase processes of chemotherapeutic agents, considering conformational and chemical characteristics of polymeric nanotransporters, from the point of view of computational chemistry. Therefore, in the present project, we studied employing advanced molecular dynamics techniques, computational modeling, and force calculations, the factors that affect the drug release process through PLA/PLGA: DSPE-PEG2000 nano-polymeric systems conjugated with COO-, NH2, and OCH3 terminals. Thus, understanding that the nature of the core of the nanosurfaces would play a fundamental role in the release of the drugs under study, where nanoparticles with PLGA-based core would present a higher affinity for drugs compared to systems with PLA-based core. On the other hand, there were indications that the aggregation of NH2 and OCH3 terminals would generate more compact systems compared to those with COO-, which could affect the release kinetics. The understanding of the structural and energetic factors that dominate the interaction and release of anticancer drugs from nanocarriers provides information to improve the rational design of Smart polymeric nanoparticles in the transport and release of drugs against colorectal cancer