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1.
ACS Chem Neurosci ; 9(11): 2554-2562, 2018 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-29771492

RESUMEN

The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized 13C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-13C]lactate, we observed that the distribution of the 13C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1-13C]lactate to [1-13C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized 13C MRS can be used to detect a variation in cerebral lactate uptake of <40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in brain metabolism.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Ácido Láctico/metabolismo , Ácido Pirúvico/metabolismo , Animales , Barrera Hematoencefálica/efectos de la radiación , Encéfalo/efectos de la radiación , Espectroscopía de Resonancia Magnética con Carbono-13 , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Ácido Láctico/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos C57BL , Ácido Pirúvico/efectos de la radiación , Ondas Ultrasónicas
2.
Ann Biomed Eng ; 45(12): 2879-2887, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28929267

RESUMEN

One of the challenges in developing sustained-release local drug delivery systems is the limited treatment volume that can be achieved. In this work, we examine the effectiveness of using low frequency, high intensity ultrasound to promote the spatial penetration of drug molecules away from the implant/injection site boundary upon release from injectable, phase inverting poly(lactic acid-co-glycolic acid) (PLGA) implants. Fluorescein-loaded PLGA solutions were injected into poly(acrylamide) phantoms, and the constructs were treated daily for 14 days with ultrasound at 2.2 W/cm2 for 10 min. The 2D distribution of fluorescein within the phantoms was quantified using fluorescence imaging. Implants receiving ultrasound irradiation showed a 1.7-5.6 fold increase (p < 0.05) in fluorescence intensity and penetration distance, with the maximum increase observed 5 days post-implantation. However, this evidence was not seen when the same experiment was also carried out in phosphate buffer saline (pH 7.4). Results suggest an active role of ultrasound in local molecular transport in the phantom. An increase of fluorescein release and penetration depth in phantoms can be accomplished through brief application of ultrasound. This simple technique offers an opportunity to eventually enhance the therapeutic efficacy and broaden the application of local drug delivery systems.


Asunto(s)
Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/efectos de la radiación , Fluoresceína/química , Ondas de Choque de Alta Energía , Ácido Láctico/química , Ácido Poliglicólico/química , Sonicación/métodos , Preparaciones de Acción Retardada/administración & dosificación , Difusión/efectos de la radiación , Fluoresceína/administración & dosificación , Ácido Láctico/efectos de la radiación , Ácido Poliglicólico/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Distribución Tisular
3.
Sci Rep ; 6: 27884, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27301578

RESUMEN

Biodegradation is a key property for biodegradable polymer-based tissue scaffolds because it can provide suitable space for cell growth as well as tailored sustainability depending on their role. Ultrashort pulsed lasers have been widely used for the precise processing of optically transparent materials, including biodegradable polymers. Here, we demonstrated the change in the biodegradation of a poly(lactic-co-glycolic acid) (PLGA) following irradiation with femtosecond laser pulses at different wavelengths. Microscopic observation as well as water absorption and mass change measurement revealed that the biodegradation of the PLGA varied significantly depending on the laser wavelength. There was a significant acceleration of the degradation rate upon 400 nm-laser irradiation, whereas 800 nm-laser irradiation did not induce a comparable degree of change. The X-ray photoelectron spectroscopy analysis indicated that laser pulses at the shorter wavelength dissociated the chemical bonds effectively, resulting in a higher degradation rate at an early stage of degradation.


Asunto(s)
Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Ácido Láctico/química , Ácido Láctico/metabolismo , Ácido Poliglicólico/química , Ácido Poliglicólico/metabolismo , Ácido Láctico/efectos de la radiación , Rayos Láser , Microscopía Electrónica de Rastreo , Ácido Poliglicólico/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Agua/química , Difracción de Rayos X
4.
ACS Appl Mater Interfaces ; 8(5): 3241-9, 2016 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-26756809

RESUMEN

Medically approved sterility methods should be a major concern when developing a polymeric scaffold, mainly when commercialization is envisaged. In the present work, poly(lactic acid) (PLA) fiber membranes were processed by electrospinning with random and aligned fiber alignment and sterilized under UV, ethylene oxide (EO), and γ-radiation, the most common ones for clinical applications. It was observed that UV light and γ-radiation do not influence fiber morphology or alignment, while electrospun samples treated with EO lead to fiber orientation loss and morphology changing from cylindrical fibers to ribbon-like structures, accompanied to an increase of polymer crystallinity up to 28%. UV light and γ-radiation sterilization methods showed to be less harmful to polymer morphology, without significant changes in polymer thermal and mechanical properties, but a slight increase of polymer wettability was detected, especially for the samples treated with UV radiation. In vitro results indicate that both UV and γ-radiation treatments of PLA membranes allow the adhesion and proliferation of MG 63 osteoblastic cells in a close interaction with the fiber meshes and with a growth pattern highly sensitive to the underlying random or aligned fiber orientation. These results are suggestive of the potential of both γ-radiation sterilized PLA membranes for clinical applications in regenerative medicine, especially those where customized membrane morphology and fiber alignment is an important issue.


Asunto(s)
Tecnología Biomédica , Ácido Láctico/química , Membranas Artificiales , Polímeros/química , Ingeniería de Tejidos/instrumentación , Óxido de Etileno/toxicidad , Rayos gamma/efectos adversos , Humanos , Ácido Láctico/efectos de la radiación , Ensayo de Materiales , Poliésteres , Polímeros/efectos de la radiación , Esterilización , Rayos Ultravioleta/efectos adversos
5.
J Biomed Mater Res B Appl Biomater ; 103(3): 596-607, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24964903

RESUMEN

Bone fixation systems made of biodegradable polymers are radiolucent, making post-operative diagnosis with X-ray imaging a challenge. In this study, to allow X-ray visibility, we separately prepared a radiopaque layer and attached it to a bioabsorbable bone plate approved for clinical use (Inion, Finland). We employed barium sulfate as a radiopaque material due to the high X-ray attenuation coefficient of barium (2.196 cm(2) /g). The radiopaque layer was composed of a fine powder of barium sulfate bound to a biodegradable material, poly(lactic-co-glycolic acid) (PLGA), to allow layer degradation similar to the original Inion bone plate. In this study, we varied the mass ratio of barium sulfate and PLGA in the layer between 3:1 w/w and 10:1 w/w to modulate the degree and longevity of X-ray visibility. All radiopaque plates herein were visible via X-ray, both in vitro and in vivo, for up to 40 days. For all layer types, the radio-opacity decreased with time due to the swelling and degradation of PLGA, and the change in the layer shape was more apparent for layers with a higher PLGA content. The radiopaque plates released, at most, 0.5 mg of barium sulfate every 2 days in a simulated in vitro environment, which did not appear to affect the cytotoxicity. The radiopaque plates also exhibited good biocompatibility, similar to that of the Inion plate. Therefore, we concluded that the barium sulfate-based, biodegradable plate prepared in this work has the potential to be used as a fixation device with both X-ray visibility and biocompatibility.


Asunto(s)
Implantes Absorbibles , Sulfato de Bario , Placas Óseas , Materiales Biocompatibles Revestidos , Medios de Contraste , Húmero/diagnóstico por imagen , Ácido Láctico , Ácido Poliglicólico , Implantes Absorbibles/efectos adversos , Absorción de Radiación , Animales , Sulfato de Bario/farmacocinética , Sulfato de Bario/efectos de la radiación , Sulfato de Bario/toxicidad , Placas Óseas/efectos adversos , Materiales Biocompatibles Revestidos/efectos de la radiación , Materiales Biocompatibles Revestidos/toxicidad , Medios de Contraste/farmacocinética , Medios de Contraste/efectos de la radiación , Medios de Contraste/toxicidad , Miembro Anterior/patología , Miembro Anterior/cirugía , Húmero/cirugía , Células L , Ácido Láctico/farmacocinética , Ácido Láctico/efectos de la radiación , Ácido Láctico/toxicidad , Masculino , Ensayo de Materiales , Ratones , Microscopía Electrónica de Rastreo , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/efectos de la radiación , Ácido Poliglicólico/toxicidad , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Conejos , Radiografía , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Rayos X
6.
Ultrason Sonochem ; 21(5): 1649-57, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24713146

RESUMEN

This study reports on the functional properties of 7% flaxseed oil/milk emulsion obtained by sonication (OM) using 20 kHz ultrasound (US) at 176 W for 1-8 min in two different delivery formulae, viz., ready-to-drink (RTD) and lactic acid gel. The RTD emulsions showed no change in viscosity after sonication for up to 8 min followed by storage up to a minimum of 9 days at 4±2 °C. Similarly, the oxidative stability of the RTD emulsion was studied by measuring the conjugated diene hydroperoxides (CD). The CD was unaffected after 8 min of ultrasonic processing. The safety aspect of US processing was evaluated by measuring the formation of CD at different power levels. The functional properties of OM gels were evaluated by small and large scale deformation studies. The sonication process improved the gelation characteristics, viz., decreased gelation time, increased elastic nature, decreased syneresis and increased gel strength. The presence of finer sono-emulsified oil globules, stabilized by partially denatured whey proteins, contributed to the improvements in the gel structure in comparison to sonicated and unsonicated pasteurized homogenized skim milk (PHSM) gels. A sono-emulsification process of 5 min followed by gelation for about 11 min can produce gels of highest textural attibutes.


Asunto(s)
Productos Lácteos/análisis , Productos Lácteos/efectos de la radiación , Aceite de Linaza/química , Aceite de Linaza/efectos de la radiación , Ultrasonido/métodos , Animales , Elasticidad/efectos de la radiación , Emulsiones , Geles/química , Geles/efectos de la radiación , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/efectos de la radiación , Concentración de Iones de Hidrógeno , Ácido Láctico/química , Ácido Láctico/efectos de la radiación , Leche/química , Leche/efectos de la radiación , Proteínas de la Leche/química , Proteínas de la Leche/efectos de la radiación , Oxidación-Reducción , Viscosidad , Proteína de Suero de Leche
7.
Mater Sci Eng C Mater Biol Appl ; 35: 426-33, 2014 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-24411397

RESUMEN

Polymeric nanofibrous composite scaffolds incorporating bioglass and bioceramics have been increasingly promising for bone tissue engineering. In the present study, electrospun poly (l-lactic acid) (PLLA) scaffolds containing dicalcium silicate (C2S) nanoparticles (approximately 300 nm) were fabricated. Using a novel ultrasonic dispersion and aging method, uniform C2S nanoparticles were prepared and they were homogenously distributed in the PLLA nanofibers upon electrospinning. In vitro, the PLLA-C2S fibers induced the formation of HAp on the surface when immersed in simulated body fluid (SBF). During culture, the osteoblastic MC3T3-E1 cells adhered well on PLLA-C2S scaffolds, as evidenced by the well-defined actin stress fibers and well-spreading morphology. Further, compared to pure PLLA scaffolds without C2S, PLLA-C2S scaffolds markedly promoted the proliferation of MC3T3-E1 cells as well as their osteogenic differentiation, which was characterized by the enhanced alkaline phosphatase (ALP) activity. Together, findings from this study clearly demonstrated that PLLA-C2S composite scaffold may function as an ideal candidate for bone tissue engineering.


Asunto(s)
Regeneración Ósea/fisiología , Compuestos de Calcio/química , Regeneración Tisular Dirigida/instrumentación , Ácido Láctico/química , Nanofibras/química , Osteoblastos/fisiología , Osteogénesis/fisiología , Polímeros/química , Silicatos/química , Andamios del Tejido , Células 3T3 , Animales , Compuestos de Calcio/efectos de la radiación , Proliferación Celular , Electroquímica/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Ácido Láctico/efectos de la radiación , Ensayo de Materiales , Ratones , Nanofibras/efectos de la radiación , Nanofibras/ultraestructura , Osteoblastos/citología , Poliésteres , Polímeros/efectos de la radiación , Rotación , Silicatos/efectos de la radiación , Sonicación
8.
Artículo en Inglés | MEDLINE | ID: mdl-24402891

RESUMEN

Liquid-core nanoparticles are promising candidates for targeted ultrasound-controlled therapy, but their acoustic detection remains challenging. High-frequency (20 to 40 MHz) tone burst sequences were implemented with a programmable ultrasound biomicroscope to characterize acoustic response from perfluorooctyl bromide-core nanoparticles with thick poly(lactide-coglycolide) (PLGA) shells. Radio-frequency signals were acquired from flowing solutions of nanoparticles with two different shell-thickness-to-particle-radius ratios, solid PLGA nanoparticles, and latex nanobeads (linear controls). Normalized fundamental (20 MHz) and second-harmonic power spectral density (PSD) increased with particle concentration and was highest for the thinnest shelled particles. The second- harmonic PSD was detectable from the nanoparticles for peak rarefactional pressures (PRP) from 0.97 to 2.01 MPa at 23 cycles and for tone bursts from 11 to 23 cycles at 2.01 MPa. Their second-harmonic¿to¿fundamental ratio increased as a function of PRP and number of cycles. Within the same PRP and cycle ranges, the second-harmonic¿to¿fundamental ratios from matched concentration solutions of latex nanobeads and solid PLGA nanoparticles was more weakly detectable but also increased with PRP and number of cycles. Nanoparticles were detectable under flow conditions in vitro using the contrast agent mode of a high-frequency commercial scanner. These results characterize linear acoustic response from the nanoparticles (20 to 40 MHz) and demonstrate potential for their highfrequency detection.


Asunto(s)
Fluorocarburos/química , Fluorocarburos/efectos de la radiación , Ondas de Choque de Alta Energía , Nanocápsulas/química , Nanocápsulas/efectos de la radiación , Sonicación/métodos , Ultrasonografía/métodos , Medios de Contraste/análisis , Medios de Contraste/química , Medios de Contraste/efectos de la radiación , Difusión/efectos de la radiación , Composición de Medicamentos/métodos , Fluorocarburos/análisis , Ácido Láctico/química , Ácido Láctico/efectos de la radiación , Tamaño de la Partícula , Ácido Poliglicólico/química , Ácido Poliglicólico/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Dosis de Radiación , Soluciones
9.
ScientificWorldJournal ; 2014: 420616, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25574485

RESUMEN

Gamma irradiation is able to affect various structural and biological properties of biomaterials In this study, a composite of Hap/PLGA-PEG and their ingredients were submitted to gamma irradiation doses of 25 and 50 KGy. Various properties such as molecular weight (GPC), thermal behavior (DSC), wettability (contact angle), cell viability (MTT assay), and alkaline phosphatase activity were studied for the composites and each of their ingredients. The results showed a decrease in molecular weight of copolymer with no change in the glass transition and melting temperatures after gamma irradiation. In general gamma irradiation can increase the activation energy ΔH of the composites and their ingredients. While gamma irradiation had no effect on the wettability of copolymer samples, there was a significant decrease in contact angle of hydroxyapatite and composites with increase in gamma irradiation dose. This study showed an increase in biocompatibility of hydroxyapatite with gamma irradiation with no significant effect on cell viability in copolymer and composite samples. In spite of the fact that no change occurred in alkaline phosphatase activity of composite samples, results indicated a decrease in alkaline phosphatase activity in irradiated hydroxyapatites. These effects on the properties of PLGA-PEG-hydroxyapatite can enhance the composite application as a biomaterial.


Asunto(s)
Durapatita/química , Durapatita/efectos de la radiación , Rayos gamma , Ácido Láctico/química , Ácido Láctico/efectos de la radiación , Polietilenglicoles/química , Polietilenglicoles/efectos de la radiación , Ácido Poliglicólico/química , Ácido Poliglicólico/efectos de la radiación , Fosfatasa Alcalina/metabolismo , Animales , Rastreo Diferencial de Calorimetría , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía en Gel , Durapatita/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Vidrio/química , Ácido Láctico/farmacología , Ratones , Microscopía Electrónica de Rastreo , Peso Molecular , Polietilenglicoles/farmacología , Ácido Poliglicólico/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Programas Informáticos , Temperatura de Transición , Humectabilidad , Difracción de Rayos X
10.
Ultrasound Med Biol ; 39(6): 1102-19, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23562023

RESUMEN

In the work described here, gene delivery using polymer microbubbles triggered by ultrasound in vitro was investigated. The effects of pressure amplitude (0-2 MPa), center frequency (1-5 MHz), pulse length (3-12,000 µs), pulse repetition frequency (5-20,000 Hz) and exposure time (0-30 s) on transfection efficiency and cell viability were examined. The effects of radiation force, calcium ion concentration and timing of treatments were also examined. Cells were successfully transfected with pressure amplitudes as low as 250 kPa. Transfection was most efficient at lower frequencies and longer pulse lengths, with a transfection efficiency of 24.2 ± 2.0% achieved using a center frequency of 1 MHz, pressure amplitude of 1 MPa, pulse length of 12,000 µs and pulse repetition frequency of 5 Hz. Gene delivery was also affected by the extracellular calcium ion concentration and the timing of treatments.


Asunto(s)
Cápsulas/efectos de la radiación , Electroporación/métodos , Ácido Láctico/efectos de la radiación , Plásmidos/química , Plásmidos/genética , Polímeros/efectos de la radiación , Sonicación/métodos , Transfección/métodos , Cápsulas/química , Humanos , Ácido Láctico/química , Células MCF-7 , Microburbujas/uso terapéutico , Plásmidos/administración & dosificación , Poliésteres , Polímeros/química
11.
Artículo en Inglés | MEDLINE | ID: mdl-25004534

RESUMEN

We designed a new film actuator, whose driving force is generated by a surface wave, which induces rotational motion. Its performance is similar to that of a rotation motor even though the new film actuator has no complex mechanical parts. To realize the film actuator, we used a poly(l-lactic acid) (PLLA) film with improved piezoelectricity. First, we theoretically investigated the necessary conditions for a surface wave to be generated on the end face of a PLLA film by the fusion of its shear piezoelectricity and resonance, and then experimentally realized this. Using the actuator made using the PLLA film, we demonstrated that the clockwise and counterclockwise rotation of an object placed on the end face of the PLLA film actuator could be freely controlled by changing the frequency of the ac voltage applied to the actuator.


Asunto(s)
Materiales Biocompatibles/química , Suministros de Energía Eléctrica , Ácido Láctico/química , Membranas Artificiales , Sistemas Microelectromecánicos/instrumentación , Polímeros/química , Transductores , Materiales Biocompatibles/efectos de la radiación , Diseño de Equipo , Ondas de Choque de Alta Energía , Ácido Láctico/efectos de la radiación , Ensayo de Materiales , Poliésteres , Polímeros/efectos de la radiación
12.
Int J Pharm ; 436(1-2): 545-54, 2012 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-22828071

RESUMEN

A main issue in controlled delivery of biotechnological products from injectable biodegradable microspheres is to preserve their integrity and functional activity after the microencapsulation process and final sterilization. The present experimental work tested different technological approaches to maintain the biological activity of an encapsulated biotechnological product within PLGA [poly (lactic-co-glycolic acid)] microspheres (MS) after their sterilization by gamma irradiation. GDNF (glial cell line-derived neurotrophic factor), useful in the treatment of several neurodegenerative diseases, was chosen as a labile model protein. In the particular case of optic nerve degeneration, GDNF has been demonstrated to improve the damaged retinal ganglion cells (RGC) survival. GDNF was encapsulated in its molecular state by the water-in-oil-in-water (W/O/W) technique or as solid according to the solid-in-oil-in-water (S/O/W) method. Based on the S/O/W technique, GDNF was included in the PLGA microspheres alone (S/O/W 1) or in combination with an antioxidant (vitamin E, Vit E) (S/O/W 2). Microspheres were sterilized by gamma-irradiation (dose of 25 kGy) at room and low (-78 °C) temperatures. Functional activity of GDNF released from the different microspheres was evaluated both before and after sterilization in their potential target cells (retinal cells). Although none of the systems proposed achieved with the goal of totally retain the structural stability of the GDNF-dimer, the protein released from the S/O/W 2 microspheres was clearly the most biologically active, showing significantly less retinal cell death than that released from either W/O/W or S/O/W 1 particles, even in low amounts of the neurotrophic factor. According to the results presented in this work, the biological activity of biotechnological products after microencapsulation and sterilization can be further preserved by the inclusion of the active molecule in its solid state in combination with antioxidants and using low temperature (-78 °C) during gamma irradiation exposure.


Asunto(s)
Antioxidantes/química , Portadores de Fármacos/química , Factor Neurotrófico Derivado de la Línea Celular Glial/química , Ácido Láctico/química , Ácido Poliglicólico/química , Vitamina E/química , Animales , Antioxidantes/administración & dosificación , Antioxidantes/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Composición de Medicamentos , Rayos gamma , Factor Neurotrófico Derivado de la Línea Celular Glial/administración & dosificación , Factor Neurotrófico Derivado de la Línea Celular Glial/efectos de la radiación , Ácido Láctico/administración & dosificación , Ácido Láctico/efectos de la radiación , Ratones , Microesferas , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Proteínas Recombinantes/efectos de la radiación , Retina/citología , Esterilización , Temperatura , Vitamina E/administración & dosificación , Vitamina E/efectos de la radiación
13.
Biofabrication ; 4(2): 025005, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22522957

RESUMEN

In this study, we explore the production of well-defined macroscopic scaffolds with two-photon polymerization (2PP) and their use as neural tissue engineering scaffolds. We also demonstrate that these 3D scaffolds can be replicated via soft lithography, which increases production efficiency. Photopolymerizable polylactic acid (PLA) was used to produce scaffolds by 2PP and soft lithography. We assessed the biocompatibility of these scaffolds using an SH-SY5Y human neuronal cell line and primary cultured rat Schwann cells (of direct relevance to the repair of nerve injuries). A Comet assay with SH-SY5Y human neuronal cells revealed minimal DNA damage after washing the photocured material for 7 days in ethanol. Additionally, thin films and 3D scaffolds of the photocured PLA sustained a high degree of Schwann cell purity (99%), enabled proliferation over 7 days and provided a suitable substrate for supporting Schwann cell adhesion such that bi-polar and tri-polar morphologies were observed. Evidence of orthogonally aligned and organized actin thin filaments and the formation of focal contacts were observed for the majority of Schwann cells. In summary, this work supports the use of PLA as a suitable material for supporting Schwann cell growth and in turn use of 3D soft lithography for the synthesis of neural scaffolds in nerve repair.


Asunto(s)
Polimerizacion/efectos de la radiación , Células de Schwann/citología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Biotecnología/instrumentación , Biotecnología/métodos , Procesos de Crecimiento Celular/fisiología , Línea Celular , Supervivencia Celular/fisiología , Células Cultivadas , Inmunohistoquímica , Ácido Láctico/química , Ácido Láctico/efectos de la radiación , Masculino , Microscopía Confocal , Microscopía Electrónica de Rastreo , Microtecnología/instrumentación , Microtecnología/métodos , Procesos Fotoquímicos , Poliésteres , Polímeros/química , Polímeros/efectos de la radiación , Ratas , Ratas Wistar
14.
Int J Nanomedicine ; 7: 1357-71, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22457594

RESUMEN

Poly(D,L-lactide-co-glycolide) and poly(D,L-lactide-co-glycolide) with poly(ethylene glycol) nanospheres (NSs) incorporating flurbiprofen (FB) were freeze-dried with several cryoprotective agents and sterilized by γ-irradiation. Only when 5.0% (w/v) hydroxypropyl-ß-cyclodextrin (HPßCD) was used, a complete resuspension by manual shaking and almost identical particle size of the NSs was obtained after freeze-drying. In vitro drug release and ex vivo corneal permeation of NSs with and without HPßCD were evaluated. The presence of HPßCD resulted in a reduction of burst effect, providing a more sustained release of the drug. A significant decrease in the FB transcorneal permeation of NSs containing HPßCD was obtained, related to the slower diffusion of FB observed in the in vitro results. The uptake mechanism of the NSs was examined by confocal microscopy, suggesting that NSs penetrate corneal epithelium through a transcellular pathway. Ocular tolerance was assessed in vitro and in vivo by the Eytex™ and Draize test, respectively. Long-term stability studies revealed that γ-irradiated NSs stored as freeze-dried powders maintained their initial characteristics. Stability studies of the resuspended NSs after 3 months of storage in the aqueous form showed that NSs were stable at 4°C, while formulations stored at 25°C and 40°C increased their initial particle size.


Asunto(s)
Flurbiprofeno/farmacocinética , Ácido Láctico/química , Nanosferas/química , Polietilenglicoles/química , Poliglactina 910/química , Ácido Poliglicólico/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Administración Oftálmica , Análisis de Varianza , Animales , Córnea/química , Córnea/efectos de los fármacos , Córnea/metabolismo , Crioprotectores/química , Estabilidad de Medicamentos , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/metabolismo , Flurbiprofeno/administración & dosificación , Flurbiprofeno/efectos adversos , Flurbiprofeno/farmacología , Liofilización , Rayos gamma , Ácido Láctico/farmacología , Ácido Láctico/efectos de la radiación , Masculino , Nanosferas/efectos de la radiación , Tamaño de la Partícula , Polietilenglicoles/farmacología , Polietilenglicoles/efectos de la radiación , Poliglactina 910/farmacología , Poliglactina 910/efectos de la radiación , Ácido Poliglicólico/farmacología , Ácido Poliglicólico/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Conejos
15.
Dent Mater J ; 30(5): 730-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21946495

RESUMEN

A bi-layered silicon-releasable membrane consisting of a siloxane-poly(lactic acid) (PLA)-vaterite hybrid material (Si-PVH) microfiber mesh and a PLA microfiber mesh has been developed by an electrospinning method for guided bone regeneration (GBR) application. The bi-layered membrane was modified to a three-laminar structure by sandwiching an additional PLA microfiber mesh between the Si-PVH and PLA microfiber meshes (Si-PVH/PLA membrane). In this study, the influence of gamma irradiation, used for sterilization, on biological properties of the Si-PVH/PLA membrane was evaluated with osteoblasts and fibroblasts. After gamma irradiation, while the average molecular weight of the Si-PVH/PLA membrane decreased, the Si-PVH/PLA membrane promoted cell proliferation and differentiation (alkaline phosphatase activity and calcification) of osteoblasts, compared with the poly(lactide-co-glycolide) membrane. These results suggest that the gamma-irradiated Si-PVH/PLA membrane is biocompatible with both fibroblasts and osteoblasts, and may have an application for GBR.


Asunto(s)
Materiales Biocompatibles/química , Regeneración Ósea/fisiología , Carbonato de Calcio/química , Regeneración Tisular Dirigida/instrumentación , Ácido Láctico/química , Membranas Artificiales , Polímeros/química , Siloxanos/química , Células 3T3 , Fosfatasa Alcalina/análisis , Animales , Materiales Biocompatibles/efectos de la radiación , Calcificación Fisiológica/fisiología , Carbonato de Calcio/efectos de la radiación , Técnicas de Cultivo de Célula , Diferenciación Celular/fisiología , Proliferación Celular , Células Cultivadas , Diseño de Equipo , Fibroblastos/fisiología , Rayos gamma , Encía/citología , Humanos , Ácido Láctico/efectos de la radiación , Ensayo de Materiales , Ratones , Microscopía Electrónica de Rastreo , Peso Molecular , Osteoblastos/fisiología , Poliésteres , Ácido Poliglicólico/química , Ácido Poliglicólico/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/efectos de la radiación , Siloxanos/efectos de la radiación , Esterilización/métodos , Mallas Quirúrgicas , Difracción de Rayos X
16.
Vox Sang ; 101(1): 35-43, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21175668

RESUMEN

BACKGROUND: A novel short-wave ultraviolet light (UVC) pathogen reduction technology (THERAFLEX UV-Platelets; MacoPharma, Mouvaux, France) without the need of any additional photoactive reagent has recently been evaluated for various bacteria and virus infectivity assays. The use of UVC alone has on the one hand been shown to reduce pathogens but may, on the other hand, have some impact on the platelet (PLT) quality. The purpose of this study was to determine the potential effects on PLT quality of pathogen inactivation treatment using the novel UVC method for PLT concentrates. STUDY DESIGN AND METHODS: Buffy-coat-derived PLTs suspended in SSP+ were irradiated with UVC light in plastic bags (MacoPharma) made of ethyl vinyl acetate, considered to be highly permeable to UVC light. The UVC-treated (test, n=8) as well as the untreated (reference, n=8) PLT units were stored in PLT storage bags composed of n-butyryl, tri n-hexyl citrate-plasticized polyvinyl chloride (MacoPharma) on a flat bed agitator for in vitro testing during 7 days of storage. RESULTS: No significant difference in PLT counts and lactate dehydrogenase between the groups was detected. During storage, glucose decreased more and lactate increased more in the test units. Statistically significant differences were found for glucose (P<0·01) and lactate (P<0·05) on day 7. ATP levels were higher (P<0·01 from day 5) in the reference units. With exception of day 7 (P<0·01 reference vs. test), hypotonic shock response reactivity was not different between groups. Extent of shape change was lower (P<0·01), and CD62P (P<0·05 day 5) was higher in the test units. CD42b and CD41/61 showed similar trends throughout storage, without any significant difference between the units. pH was maintained at >6·8 (day 7) and swirling remained at the highest level (score = 2) for all units throughout storage. CONCLUSION: Our results suggest that irradiation with UVC light has a slight impact on PLT in vitro quality and appears to be insignificant with regard to current in vitro standards.


Asunto(s)
Adenosina Trifosfato/metabolismo , Plaquetas/metabolismo , Plaquetas/efectos de la radiación , Conservación de la Sangre/métodos , Glucosa/metabolismo , Ácido Láctico/metabolismo , Rayos Ultravioleta , Adenosina Trifosfato/efectos de la radiación , Bacterias/crecimiento & desarrollo , Bacterias/efectos de la radiación , Plaquetas/microbiología , Glucosa/efectos de la radiación , Humanos , Integrina beta3/metabolismo , Integrina beta3/efectos de la radiación , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/efectos de la radiación , Ácido Láctico/efectos de la radiación , Selectina-P/metabolismo , Selectina-P/efectos de la radiación , Recuento de Plaquetas , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Complejo GPIb-IX de Glicoproteína Plaquetaria/efectos de la radiación , Glicoproteína IIb de Membrana Plaquetaria/metabolismo , Glicoproteína IIb de Membrana Plaquetaria/efectos de la radiación
17.
Radiother Oncol ; 96(1): 123-30, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20542345

RESUMEN

PURPOSE: To correlate non-invasively acquired radiobiologically relevant magnetic resonance (MR) parameters with functional histology and tumor control doses (TCD(50)). MATERIALS AND METHODS: The MR parameters relative perfusion, re-oxygenation and lactate (Lac) concentration from eight human xenograft squamous tumor lines were compared with the histologically acquired pimonidazole hypoxic fraction, the perfused vessel area and TCD(50). RESULTS: Good spatial correlation in the parameter maps could be observed between the pimonidazole staining and tumor regions, which can be reoxygenated when breathing carbogen. A strong positive correlation (R=0.74) was found between whole tumor pimonidazole hypoxic fraction and re-oxygenation, as one would expect. A good correlation was also observed between Lac concentration and re-oxygenation (R=0.71) and between TCD(50) and re-oxygenation (R=0.64), whereas Lac and TCD(50) showed a moderate relation (R=0.44). The in vivo measurement of relative perfusion could be validated to reflect the perfused vessel area (R=0.63). No correlation was detected between perfusion and re-oxygenation or TCD(50). CONCLUSIONS: Lac and re-oxygenation were shown to be pretreatment predictive markers independent from the pathophysiological changes induced during a fractionated course of radiotherapy. These parameters hold promise to be acquired non-invasively with results just a few minutes after measurement and to tailor radiotherapy to individual patterns of a tumor microenvironment.


Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Fraccionamiento de la Dosis de Radiación , Ácido Láctico/metabolismo , Imagen por Resonancia Magnética/métodos , Animales , Hipoxia de la Célula/efectos de la radiación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta en la Radiación , Humanos , Inmunohistoquímica , Ácido Láctico/efectos de la radiación , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Nitroimidazoles/farmacología , Consumo de Oxígeno/efectos de la radiación , Dosis de Radiación , Fármacos Sensibilizantes a Radiaciones/farmacología , Sensibilidad y Especificidad , Trasplante Heterólogo
18.
Ultrason Sonochem ; 17(5): 752-5, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20226709

RESUMEN

Mild and efficient Fischer esterification reactions of lactic acid with a variety of straight chain aliphatic alcohols, cyclohexanol and benzyl alcohol were successfully performed using two novel Brønsted acidic ionic liquids that bear an aromatic sulfonic acid group on the imidazolium or pyridinium cation under ultrasound irradiation. These reactions carried out smoothly with good to excellent conversion rate (78-96%) and satisfactory yields (73-92%) in shorter reaction time (4-6h) at room temperature when the amount of ionic liquids was 20 mol%. These ionic liquids could be recovered readily and recycled five times without any significant loss in their catalytic activity.


Asunto(s)
Líquidos Iónicos/química , Líquidos Iónicos/efectos de la radiación , Ácido Láctico/síntesis química , Ácido Láctico/efectos de la radiación , Sonicación , Sulfatos/química , Sulfatos/efectos de la radiación , Ácidos/química , Ácidos/efectos de la radiación , Ésteres/química , Ésteres/efectos de la radiación , Solventes/química , Solventes/efectos de la radiación
19.
Ultrason Sonochem ; 17(5): 902-8, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20163978

RESUMEN

In this work poly(D,L-lactide-co-glycolide) (PLGA) and a poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) composite processed in an ultrasonic field at higher (25 degrees C) and lower (8 degrees C) temperatures were studied with respect to the molecular properties of the obtained materials. The processing of the PLGA and the PLGA/HAp composite in an ultrasonic field resulted in a change of molar mass averages of the polymer/polymeric part of these materials, while an amorphous structure and a 50:50 lactide-to-glycolide co-monomer ratio were preserved without the formation of crystalline oligomers. However, mobility of polymeric chains obtained after ultrasonic processing was lower indicating ordering the structure of polymeric chains as a result of processing. Additionally, it was observed that the mobility of the PLGA macromolecules was lower within the composite in comparison with the mobility of the chains within the PLGA alone in the case when both were obtained after ultrasonic processing. This was a consequence of the structure formation through the interactions between the PLGA and the HAp. Based on these results different degradation rate of PLGA in composite can be expected, which is important in the application of this material for the controlled drug delivery of medicaments.


Asunto(s)
Materiales Biocompatibles/química , Materiales Biocompatibles/efectos de la radiación , Durapatita/química , Durapatita/efectos de la radiación , Ácido Láctico/química , Ácido Láctico/efectos de la radiación , Ácido Poliglicólico/química , Ácido Poliglicólico/efectos de la radiación , Sonicación , Sustancias Macromoleculares/química , Sustancias Macromoleculares/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
20.
Eur Surg Res ; 44(2): 102-10, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20110717

RESUMEN

AIM: The purpose was to evaluate soft-tissue healing after poly(lactic acid) (PLA(94)) mesh implantation in a rat model. METHODS: Full-thickness abdominal wall defects were created in 108 Wistar rats, and reconstructed with 83 PLA(94) and 25 lightweight polypropylene (PPL) meshes. The meshes were previously gamma-ray sterilised with 25, 75 or 125 kGy to accelerate PLA(94) degradation. RESULTS: The inflammatory response in PLA(94) was significantly less pronounced and collagen organisation significantly better than in PPL. The higher the level of gamma-radiation, the higher the incidence of abdominal wall herniation (22.2, 31.3 and 52.6% with 25, 75 and 125 kGy, respectively). No herniation occurred in the PPL group. Tensile strength was dramatically reduced after gamma-ray-sterilised PLA(94) mesh implantation. CONCLUSION: The gamma-ray-sterilised PLA(94) mesh was poor in preventing abdominal wall hernia recurrences in a rat model.


Asunto(s)
Inflamación/prevención & control , Ácido Láctico/uso terapéutico , Membranas Artificiales , Polímeros/uso terapéutico , Cicatrización de Heridas/fisiología , Animales , Desinfección , Rayos gamma , Hernia Abdominal/epidemiología , Hernia Abdominal/patología , Inflamación/patología , Ácido Láctico/efectos de la radiación , Poliésteres , Polímeros/efectos de la radiación , Ratas , Ratas Wistar , Heridas y Lesiones/mortalidad , Heridas y Lesiones/patología
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