ABSTRACT
Although, antineoplastic therapies have now been developed reduction of tumor progression,itis necessarytofind new therapeutic alternatives to suppress angiogenesis.Thus celecoxib (Cx) has been used for its antiangiogenic action in combination with certain polymeric compounds such as poly (lactic co-glycolic acid) (PLGA) acid, which help to improve the bioavailability and avoid effects of long drug administrations. For this purpose we used a murine tumor modelinduced by mammary adenocarcinoma cells resistant to chemotherapy (TA3-MTXR). CX/PLGA inhibits the microvascular density, VEGF expression and cell proliferationinaddition to increased apoptosis (P <0.0001). Cx reduces tumor progression in a concentration of 1000 ppm associated with PLGA, reducing cell proliferation, the presence of VEGF and promoting apoptosis of multiresistant TA3 tumor cells.
Si bien actualmente se han desarrollado terapias antineoplásicas que permiten reducir de cierta manera el avance tumoral, es necesario buscar nuevas alternativas terapéuticas que permitan suprimir la angiogénesis. Es así como el Celecoxib (Cx) ha sido utilizado por su acción antiangiogénica en combinación con algunos compuestos poliméricos, tal como el ácido poli (láctico co-glicólico) (PLGA), el cual ayudaría a mejorar la biodisponibilidad y evitaría efectos derivados de largas administraciones del fármaco. Para tal efecto se ha utilizado un modelo tumoral murino, inducido por células tumorales de adenocarcinoma mamario resistente a la quimioterapia (TA3-MTXR). Los resultados indican que CX/PLGA inhibe la microvascularización, expresión de VEGF y la proliferación celular además del aumento de la apoptosis (P<0,0001). El efecto antitumoral del Cx está bien reportado en la literatura; este sumado a la microencapsulación con PLGA, aportarían un sistema de administración útil, ya que nos otorga una administración sostenida en el tiempo, los cual podría ayudar a mantener los niveles de droga durante un período más prolongado, lo cual sería beneficioso en la terapia tumoral.
Subject(s)
Animals , Female , Mice , Antineoplastic Agents/administration & dosage , Celecoxib/administration & dosage , Neovascularization, Pathologic/drug therapy , Apoptosis/drug effects , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Drug Delivery Systems , Immunohistochemistry , Lactic Acid/administration & dosage , Neoplasm Invasiveness/prevention & control , Polyglycolic Acid/administration & dosage , Polymers/administration & dosage , Vascular Endothelial Growth Factor A/drug effectsABSTRACT
La proteína morfogenética ósea (BMP), es una proteína endógena que ha mostrado efectos significativos en la promoción de la formación ósea. El uso de BMP ha sido descrito en la reconstrucción de defectos óseos de origen traumáticos y patológicos, incluyendo la fisura alveolar, el aumento de reborde alveolar, la elevación de seno maxilar, el injerto de alveolo post-extracción, y la cirugía perimplantaria entre otros. A pesar de las ventajas asociadas al uso de BMP y que en la actualidad se aplica en combinación con matrices de colágeno, ciertas propiedades tales como su baja resistencia mecánica y su elevada tasa de liberación inicial disminuyen su eficacia en la formación ósea. En este contexto, el desarrollo de nuevos sistemas de liberación prolongada de BMP que permitan la quimiotaxis de células mesenquimáticas y su posterior diferenciación a osteoblastos representa un desafío con alto potencial clínico para la estimulación de la formación ósea. En este trabajo, se describe el uso de BMP en la reconstrucción de fisuras alveolares y en particular se discuten las ventajas de su administración en micropartículas poliméricas comosistemas de liberación de BMP (rhBMP-2) con promisorias aplicaciones en la estimulación de la formación ósea.
Bone morphogenetic protein (BMP) is an endogenous protein that has shown significant effects in the promotion of bone formation. BMP also has been described in the reconstruction of traumatic and pathological bone defects, including alveolar cleft, alveolar ridge augmentation, maxillary sinus elevation, and applications in post-extraction alveolus graft, and peri-implant surgery among others. Despite the advantages associated with the use of BMP, currently is applied in combination with collagen matrices, which has certain properties such as low mechanical resistance and a high burst initial release that diminish its effectiveness in bone formation. In this context, the development of novel systems with greater mechanical resistance and prolonged release of BMP, that lead to chemotaxis of mesenchymal cells, following by its differentiation to osteoblasts represents a major challenge that holds outstanding clinical potential for the stimulation of bone formation. In this paper, we describe the use of BMP for the reconstruction of alveolar clefts, and its advantages being administrated in polymeric microparticles as sustain release system with promising applications in the stimulation of bone formation.
Subject(s)
Humans , Alveolar Process/surgery , Bone Morphogenetic Protein 2/therapeutic use , Bone Morphogenetic Proteins/therapeutic use , Recombinant Proteins/therapeutic use , Bone Regeneration/drug effects , Cleft Palate/surgery , NanoparticlesABSTRACT
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.
Subject(s)
Cosmetics/pharmacokinetics , Dermatology/trends , Nanotechnology/trends , Polymers/pharmacokinetics , Skin/drug effects , Cosmetic Techniques/trends , Drug Delivery Systems , Skin/anatomy & histology , Technology, PharmaceuticalABSTRACT
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 ± 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.
Subject(s)
Magnetite Nanoparticles/chemistry , Magnetic Resonance Imaging , Drug Delivery Systems , Contrast Media , Microscopy, Electron, Transmission , Nanomedicine , Magnetite Nanoparticles/analysis , Magnetite Nanoparticles/ultrastructure , Magnetic Iron Oxide Nanoparticles/chemistry , Hyperthermia, InducedABSTRACT
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 μm. The encapsulation efficiency was 39.5 +/- 1.1 percent 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 > 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.
Subject(s)
Animals , Cattle , Cephalosporins/administration & dosage , Bacterial Infections/drug therapy , Bacterial Infections/veterinary , Polyesters/administration & dosage , Anti-Bacterial Agents/administration & dosage , Chromatography, High Pressure Liquid , Escherichia coli , Microscopy, Electron, ScanningABSTRACT
The administration of microencapsulated drug in a matrix acid poly(lactic-co-glycolic acid) (PLGA) by intramuscular (IM) in humans has been approved by the FDA for various applications though it is not clear what effect they have on the morphological parameters of muscle tissue. The aim of this study was to analyze the morphological changes in the skeletal muscle tissue with their use. We used 12 adult female Sprague Dawley rats (Rattus novergicus) that were injected into their right gastrocnemius muscle belly with: sterile vehicle solution (G1, n = 4), 0.5 mg PLGA microparticle (G2, n = 4) and 0.75 mg PLGA microparticle (G3, n = 4), both dissolved in a sterile vehicle solution. At 14 days post injection the number and diameter of muscle fibers, the level of inflammation and histology appearance in terms of organization of muscle fibers, cellular distribution, tissue morphology and the presence of polymer waste were determined and the results between the groups compared. The administration of the compound in a single dose did not alter the morphometric parameters (number and diameter of muscle fibers) despite generating a mild inflammation in the tissue associated with the presence of polymeric residues, suggesting that the PLGA microparticles were well tolerated by the muscle tissue at concentrations tested (0.5 and 0.75 mg).
La administración de fármacos encapsulados en micropartículas de ácido poli-láctico/glicólico (PLGA) por vía intramuscular (IM) ha sido aprobada por FDA para su uso en seres humanos con variadas aplicaciones, no estando claro el efecto que tienen sobre los parámetros morfológicos del tejido muscular. El objetivo de este estudio fue analizar los cambios morfológicos en el tejido muscular esquelético. Se utilizaron 12 ratas (Rattus novergicus) hembras de la cepa Sprague Dawley, las cuales fueron inyectadas en el vientre del músculo gastrocnemio derecho con: solución vehículo estéril (G1, n=4) y con micropartículas 0,5 mg (G2, n=4) y 0,75 mg de PLGA (G3, n=4) ambas disueltas en solución vehículo estéril. A los 14 días post inyección se determinó el número y diámetro de fibras musculares, el nivel de inflamación y el aspecto histológico en términos de organización de fibras musculares, así como la distribución y morfología celular del tejido conjuntivo y presencia de residuos poliméricos, comparándose los resultados entre los grupos de estudio. La administración del compuesto en una sola dosis no modificó los parámetros morfométricos (número y diámetro de las fibras musculares), a pesar de generar una inflamación leve en el tejido, asociado a la presencia de residuos poliméricos, lo que sugiere que microesferas de PLGA son bien toleradas por el tejido muscular en las concentraciones probadas (0,5 and 0,75 mg).