135 research outputs found
Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride
A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f2 = 69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon–Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established
An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines
The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity
Determination of the spatiotemporal dependence of Pseudomonas aeruginosa biofilm viability after treatment with NLC-colistin
The emergence of colistin-resistant Pseudomonas aeruginosa in cystic fibrosis (CF) patients, particularly after long-term inhalation treatments, has been recently reported. Nanoencapsulation may enable preparations to overcome the limitations of conventional pharmaceutical forms. We have determined the time-dependent viability of P. aeruginosa biofilms treated with both free and nanoencapsulated colistin. We also examined the relationship between the optimal anti-biofilm activity of nanostructured lipid carrier (NLC)-colistin and the structural organization of the biofilm itself. The results showed the more rapid killing of P. aeruginosa bacterial biofilms by NLC-colistin than by free colistin. However, the two formulations did not differ in terms of the final percentages of living and dead cells, which were higher in the inner than in the outer layers of the treated biofilms. The effective anti-biofilm activity of NLC-colistin and its faster killing effect recommend further studies of its use over free colistin in the treatment of P. aeruginosa infections in CF patients
Influence of data sources and processing methods on theoretical river network quality
ABSTRACT: Stream ecosystem research and water resource management need to be considered over broad spatial scales. Moreover, the investigation of the spatial configuration and habitat characteristics of streams requires an accurate and precise spatial framework to reflect a catchment's physical reality that can successfully explain observed patterns at smaller scales. In this sense, geographic information systems represent an essential tool to satisfy the needs of researchers and managers. Specifically, theoretical river networks (TRNs) extracted from digital elevation models (DEMs) have become much more common in recent years, as they can provide a suitable spatial network and hierarchical organisation to sort out river ecosystem information from reach to catchment levels. Nevertheless, the quality of the extracted TRN depends greatly on the spatial resolution of the DEM and the methodology used in the network extraction processes. In this study, we compare the quality of 9 TRNs extracted from DEMs with different spatial resolutions ranging from regional (5 m) to national (25 m) and global scales (90 m) using the ArcHydro, Hec-GeoHMS and Netstream software packages. To achieve our goal, we compared (i) the DEM-derived slope; (ii) the spatial accuracy of the TRNs in relation to a control river network; (iii) the structure of the TRNs through analysis of the number of river segments, average river segment length and total river length by stream order, drainage density and the mean upstream slope throughout the TRN; and (iv) the ability of variables derived from TRNs to discriminate among stream types classified according to flow type and substrate composition. We demonstrated that not only DEM spatial resolution but also the DEM data source and raster creation process exert an important influence on terrain characteristics derived from DEMs and TRN properties. Moreover, TRNs extracted with NetStream generally showed better performance than those extracted with ArchHydro and HecGeoHMS. Nevertheless, river network extraction quality, DEM spatial resolution and extraction algorithms exhibit complex relationships due to the large number of interacting factors.The work described in this paper is part of a research project financed by the National Plan (2008-2011) for Research in Science & Technology of the Spanish Government (Project CTM2009-07447). The authors appreciate the valuable suggestions of anonymous reviewers that greatly improvement the document
Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research
There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants) as well as the immunostimulatory effect of the formulation components (immunostimulants) modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI) and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.This project was partially supported by the "Ministerio de Ciencia e Innovacion" (SAF2007-66115), the University of the Basque Country (UPV/EHU) (UFI 11/32), and FEDER funds. E. Mata thanks the Basque Government for a fellowship grant
Evaluation of New Formulations of Antihelmintic Drugs for the Treatment of Schistosomiasis
La esquistosomosis es una enfermedad causada por parásitos trematodos del género Schistosoma. Afecta principalmente a áreas tropicales y subtropicales, siendo un principal problema de salud mundial por su alta incidencia en estas regiones. Una de las especies de mayor importancia, por su prevalencia y gravedad, es la causada por Schistosoma mansoni,responsable de la esquistosomosis intestinal. El tratamiento de elección esel praziquantel, con altas tasas de eficacia clínica. Sin embargo, el fármacono impide la reinfección y se ha observado fallos terapéuticos en zonasendémicas. Por ello, se hace necesaria la búsqueda de alternativas terapéuticas.El objetivo de este estudio es evaluar dos tipos de formulaciones denanopartículas de praziquantel (tipo A y tipo S) y un tratamiento alternativocomo la ivermectina mediante ensayos in vitro sobre adultos de S. mansoni.Los resultados demostraron que el tratamiento con nanopartículas presentauna eficacia similar o mayor que el empleo de praziquantel comercial. Sinembargo, el tratamiento con ivermectina no aportó evidencias de mayoreficacia. Trabajos futuros irán encaminados a evaluar estas formulacionesen otras fases del ciclo biológico, así como a realizar estudios in vivo enanimales de experimentación.Palabras clave: Schistosoma; esquistosomosis; praziquantel; nanopartículas;ivermectina.Fil: Castrillejo, Sergio A.. Universidad de Salamanca; EspañaFil: López Abán, Julio. Universidad de Salamanca; EspañaFil: Muro, Antonio. Universidad de Salamanca; EspañaFil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Pastor Navarro, Marta. Universidad del País Vasco; España. Centro de Investigación Biomédica en Red; EspañaFil: Pedraz, José Luis. Universidad del País Vasco; España. Centro de Investigación Biomédica en Red; Españ
Influence of data sources and processing methods on theoretical river network quality
Stream ecosystem research and water resource management need to be considered over broad spatial scales. Moreover, the investigation of the spatial configuration and habitat characteristics of streams requires an accurate and precise spatial framework to reflect a catchment's physical reality that can successfully explain observed patterns at smaller scales. In this sense, geographic information systems represent an essential tool to satisfy the needs of researchers and managers. Specifically, theoretical river networks (TRNs) extracted from digital elevation models (DEMs) have become much more common in recent years, as they can provide a suitable spatial network and hierarchical organisation to sort out river ecosystem information from reach to catchment levels. Nevertheless the quality of the extracted TRN depends greatly on the spatial resolution of the DEM and the methodology used in the network extraction processes. In this study, we compare the quality of 9 TRNs extracted from DEMs with different spatial resolutions ranging from regional (5 m) to national (25 m) and global scales (90 m) using the ArcHydro, Hec-GeoHMS and Netstream software packages. To achieve our goal, we compared (i) the DEM-derived slope; (ii) the spatial accuracy of the TRNs in relation to a control river network; (iii) the structure of the TRNs through analysis of the number of river segments, average river segment length and total river length by stream order, drainage density and the mean upstream slope throughout the TRN; and (iv) the ability of variables derived from TRNs to discriminate among stream types classified according to flow type and substrate composition. We demonstrated that not only DEM spatial resolution but also the DEM data source and raster creation process exert an important influence on terrain characteristics derived from DEMs and TRN properties. Moreover, TRNs extracted with NetStream generally showed better performance than those extracted with ArchHydro and HecGeoHMS. Nevertheless, river network extraction quality, DEM spatial resolution and extraction algorithms exhibit complex relationships due to the large number of interacting factors.La investigación de los ecosistemas acuáticos continentales y la gestión de recursos hídricos necesitan ser considerados a escalas espaciales que abarquen grandes territorios. Así mismo, el estudio de la configuración espacial de los sistemas fluviales y las características del hábitat requieren de un marco espacial preciso con el que explicar los patrones observados a pequeña escala a partir de las características físicas de la cuenca. En este sentido, los sistemas de información geográfica representan una herramienta esencial. Específicamente, la extracción de redes fluviales teóricas (RFT) a partir de modelos digitales de elevación (MDEs) ha sufrido una importante expansión y desarrollo en los últimos años. Las RTF, proporcionan un marco espacial adecuado e integran la estructura jerárquica de los ecosistemas fluviales, de tal modo que pueden englobar información a diferentes escales espaciales, desde el nivel de cuenca al de tramo. Sin embargo, la calidad de las RFTs depende, en gran medida, de la resolución espacial de los MDE y de los métodos utilizados en el proceso de extracción de la red. En este estudio hemos comparado la calidad de 9 RFTs obtenidas a partir de MDEs con diferentes resoluciones espaciales, que van desde la escala regional (5 m), nacional (25 m) hasta global (90 m) mediante ArcHydro, HecGeoHMS y NetStream.Para lograr nuestro objetivos hemos comparado (i) las características de la pendiente derivada de los MDEs, (ii) la precisión espacial de las RFT en relación a una red fluvial control, (iii) la estructura de los RTFs mediante el análisis del número de segmentos, la longitud media y total de los segmentos de cada orden fluvial, la densidad de drenaje y la pendiente media de la cuenca a lo largo de la RFT y (iv) la capacidad de variables físicas derivadas de las RFT para discriminar entre tipos de ríos clasificados con base en el tipo de flujo y la composición del sustrato. Los resultados obtenidos han demostrado que la calidad de las características físicas derivadas del MDE y las propiedades de las RFTs no están determinadas únicamente por la resolución espacial del MDE, sino que el tipo de dato del que provenga el MDE y el proceso de generación del mismo ejercen una gran influencia. Además, NetStream ha generado, por lo general, unas RTFs más precisas que ArcHydro y HecGeoHMS. Sin embargo, la interacción de un gran número de factores durante el proceso de generación de redes hace que las relaciones entre la calidad de las mismas, la resolución espacial de los MDE y los algoritmos utilizados sean complejas
Gene Therapy for Cystic Fibrosis: Hurdles to Overcome for Successful Clinical Translation
Cystic fibrosis (CF) is a genetic disease that hampers the lung function. Despite that the main defective gene has been deeply characterized, some relevant concerns still need to be resolved before considering gene therapy as a realistic medical choice. One of the major issues that need to be strongly considered in order to succeed in the search for an effective gene therapy approach for CF is the design of the appropriate genetic material to be delivered. Other relevant factors to take into consideration include the design of safe and effective gene delivery systems, the biological barriers that need to be overcome in order to reach the nucleus of the target cells, and the problems related to the design of a drug formulation suitable for lung delivery purposes. Furthermore, some problems related to the commercialization of gene therapy products also need to be resolved. In this chapter, we discuss the up-to-date strategies to overcome such hurdles in order for gene therapy to become a routine treatment modality for CF
Encapsulation of Oleuropein in Nanostructured Lipid Carriers: Biocompatibility and Antioxidant Efficacy in Lung Epithelial Cells
Oxidative damage has been linked to a number of diseases. Oleuropein (OLE), a natural occurring polyphenol from olive leaves (Olea europaea L.), is known to be a potent antioxidant compound with inherent instability and compromised bioavailability. Therefore, in this work, nanostructured lipid carriers (NLCs) were proposed for OLE encapsulation to protect and improve its antioxidant efficacy. The lipid matrix, composed of olive oil and Precirol, was optimized prior to OLE encapsulation. The characterization of the optimized oleuropein-loaded NLCs (NLC-OLE) showed a mean size of 150 nm, a zeta potential of −21 mV, an encapsulation efficiency of 99.12%, sustained release profile, and improved radical scavenging activity. The cellular in vitro assays demonstrated the biocompatibility of the NLCs, which were found to improve and maintain OLE antioxidant efficacy in the A549 and CuFi-1 lung epithelial cell lines, respectively. Overall, these findings suggest a promising potential of NLC-OLE to further design a pulmonary formulation for OLE delivery in lung epithelia.A.H.-C. thanks the Spanish Ministry of Economy and Competitiveness for the Industrial Doctorate fellowship grant (DI-15-07513). This work was done under the R&D projects of BIOSASUN and supported by the University of the Basque Country (UPV/EHU) and the Basque Country Government (Grupos Consolidados, No. IT907-16 to J.L.P.)
- …