Daniel Bachiller - Academia.edu (original) (raw)

Papers by Daniel Bachiller

Research paper thumbnail of Nanoparticule lipidique de pol ymyxine

The present invention is related to a lipid nanoparticle comprising at least one antibiotic from ... more The present invention is related to a lipid nanoparticle comprising at least one antibiotic from the polymyxin family, a lipid fraction and one or more surfactants. The invention is also related to the use of the nanoparticle in the prevention and/or treatment of respiratory tree infectionsPeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)B1 Patente sin examen previ

Research paper thumbnail of Lipid nanoparticle of polymyxin

A lipid nanoparticle that includes at least one antibiotic from the polymyxin family, a lipid fra... more A lipid nanoparticle that includes at least one antibiotic from the polymyxin family, a lipid fraction, and one or more surfactants. The lipid nanoparticle is useful in the prevention and/or treatment of respiratory tree infectionsPeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Research paper thumbnail of 834 Correspondence

in red color overlaying a grayscale light image of the whole mouse (A-C), 10- m m sections of par... more in red color overlaying a grayscale light image of the whole mouse (A-C), 10- m m sections of parenchy-mal organs (D). Scale bars correspondent to 1 cm (A-C) and 20 m m (D). Analyses of time dynamics of iPS distribution through the paren-chymal organs might allow for the quantifi cation of their relative homing capabilities in the organ of interest and, thereby, better clarifi cation of their role in the different pathologic processes.

Research paper thumbnail of Patterning by genes expressed in Spemann's organizer

Cold Spring Harbor symposia on quantitative biology, 1997

... EM DE ROBERTIS, S. KIM, L. LEYNS, S. PICCOLO, D. BACHILLER, E. AGIUS, JA BELO, A. YAMAMOTO, A... more ... EM DE ROBERTIS, S. KIM, L. LEYNS, S. PICCOLO, D. BACHILLER, E. AGIUS, JA BELO, A. YAMAMOTO, A. HAINSKI-BROUSSEAU, B. BRIZUELA ... 1997; for review, see Bouwmeester and Leyns 1997), have led to the unex-pected realization that the vertebrate head may be in ...

Research paper thumbnail of Nanopartícula lipídica de polimixina

La presente invencion se relaciona con una nanoparticula lipidica que comprende al menos un antib... more La presente invencion se relaciona con una nanoparticula lipidica que comprende al menos un antibiotico de la familia de las polimixinas, una fraccion lipidica y uno o mas tensioactivos,y el uso de la nanoparticula en la prevencion y/o tratamiento de infecciones del arbol respiratorio.

Research paper thumbnail of Lipid nanoparticle of polymyxin

The invention relates to a lipid nanoparticle comprising at least one antibiotic from the polymyx... more The invention relates to a lipid nanoparticle comprising at least one antibiotic from the polymyxin family, a lipid fraction and one or more surfactants, and to the use of the nanoparticle in the prevention and/or treatment of infections in the respiratory system.

Research paper thumbnail of Molécula de ácido nucleico, proteína de fusión y método para modificar el material genético de una célula

La presente invencion se relaciona con una molecula de acido nucleico que codifica una proteina d... more La presente invencion se relaciona con una molecula de acido nucleico que codifica una proteina de fusion, comprendiendo la molecula de acido nucleico en sentido 5´---3´ de transcripcion al menos una secuencia de acido nucleico que codifica un dominio de union al ADN, y una secuencia de acido nucleico que codifica un dominio catalitico del tipo FokI, en donde en su extremo 3´comprende una secuencia de acido nucleico que codifica un peptido que comprende entre 18 y 23 aminoacidos, con una proteina de fusion obtenible por ejemplo de la transcripcion de dicha molecula, y con un metodo para modificar el material genetico de una celula mediante el uso de dicha molecula o proteina.

Research paper thumbnail of Chordin and noggin promote organizing centers of forebrain development in the mouse

Development, 2002

In this study we investigate the roles of the organizer factors chordin and noggin, which are ded... more In this study we investigate the roles of the organizer factors chordin and noggin, which are dedicated antagonists of the bone morphogenetic proteins(BMPs), in formation of the mammalian head. The mouse chordin and noggin genes(Chrd and Nog) are expressed in the organizer (the node) and its mesendodermal derivatives, including the prechordal plate, an organizing center for rostral development. They are also expressed at lower levels in and around the anterior neural ridge, another rostral organizing center. To elucidate roles of Chrd and Nog that are masked by the severe phenotype and early lethality of the double null, we have characterized embryos of the genotype Chrd-/-;Nog+/-. These animals display partially penetrant neonatal lethality, with defects restricted to the head. The variable phenotypes include cyclopia,holoprosencephaly, and rostral truncations of the brain and craniofacial skeleton. In situ hybridization reveals a loss of SHH expression and signaling by the prechor...

Research paper thumbnail of Safety and effectiveness of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) against P. aeruginosa: in vitro and in vivo studies following pulmonary and intramuscular administration

Nanomedicine: Nanotechnology, Biology and Medicine, 2019

Research paper thumbnail of Conservation of a functional hierarchy between mammalian and insect Hox/HOM genes

The EMBO Journal, 1994

3Corresponding author D.Bachiller and A.Macias have contributed equally to this work Communicated... more 3Corresponding author D.Bachiller and A.Macias have contributed equally to this work Communicated by G.Morata We have generated several transgenic Drosophila strains containing different mouse Hox genes under heat shock control and studied how their generalized expression affects Drosophila larval patterns. We find that they have spatially restricted effects which correlate with their genetic order and expression pattern in the mouse; as they are expressed more posteriorly in the mouse, they have more extensive effects in Drosophila. The generalized expressions of Hoxd-8 and d-9 modify Drosophila anterior head segment(s), but have no effect in the rest of the body. Hoxd-10 expression affects head and thorax, but not the abdomen. Finally, Hoxd-11 alters head, thorax and abdomen. The developmental effect of the Hox genes consists of a homeotic transformation of the affected segment(s), which exhibit a 'ground' pattern similar to that obtained in the absence of homeotic information, suggesting that Hox genes are able to inactivate Drosophila homeotic genes, but do not specify a pattern of their own. A partial exception is Hoxd-11 which, even though it has a general suppressing effect, can also activate the resident Abdominal-B and empty spiracles genes in ectopic positions. Our results strongly suggest a general conservation of the functional hierarchy of homeotic genes that correlates with genetic order and expression patterns.

Research paper thumbnail of Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis

International journal of pharmaceutics, Jan 10, 2016

Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most... more Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most prevalent. As a way to fight against this infection, nanotechnology has emerged over the last decades as a promising alternative to overcome resistance to antibiotics in infectious diseases. The goal of this work was to elaborate and characterize lipid nanoparticles for pulmonary delivery of tobramycin. Tobramycin-loaded nanostructured lipid carriers (Tb-NLCs) were prepared by hot melt homogenization technique. In addition, nanoparticles labeled with infrared dye (IR-NLCs) were used to investigate their in vivo performance after pulmonary administration. Tb-NLCs displayed a mean diameter size around 250nm, high drug encapsulation (93%) and sustained release profile. Tb-NLCs showed to be active against clinically isolated P. aeruginosa. Moreover, Tb-NLCs did not decrease cell viability and were able to overcome an artificial mucus barrier in the presence of mucolytics agents. During the ...

Research paper thumbnail of In vivo Langzeit-Evaluierung der Homing-Eigenschaften induzierter Stammzellen

Einführung Die Möglichkeit, somatische Zellen in induzierte pluripotente Stammzellen (iPS-Zellen)... more Einführung Die Möglichkeit, somatische Zellen in induzierte pluripotente Stammzellen (iPS-Zellen) umzuprogrammieren, eröffnet komplett neue Wege für die regenerative Medizin. Diese Zellen sind außergewöhnlich vielversprechend für die Reparatur von geschädigten Geweben und Organen (Sueblinvong and Weiss, 2010). Eine geeignete Zelltherapie eröffnet nun das große Potenzial, neue Behandlungsmethoden für eine Vielzahl von Erkrankungen wie Krebs zu entwickeln. Dabei ist der therapeutische Nutzen abhängig von der erfolgreichen Homing und Wiederbesiedlung von iPS-Zellen (Gonzalez, et al., 2011). In der Stammzellforschung wurden "Homing", als die Fähigkeit von Stammzellen beschrieben, zu ihrem Bestimmungsort oder zu ihrer "Nische" zu gelangen. Die ersten Transplantationen mit multipotenten Knochmarkszellen vor über 30 Jahren verdeutlichten die Tragweite eines effektiven Homings. In diesem Verfahren wurden gespendete Knochenmarkzellen, die ein neues Blut-produzierendes Sys...

Research paper thumbnail of Application of infrared protein to in vivo imaging of transplated cell migration

Research paper thumbnail of Stem cells based therapy for lung pathologies and blood circulation

There is a growing interest in the development of new Stem Cells (SCs) based therapeutic strategi... more There is a growing interest in the development of new Stem Cells (SCs) based therapeutic strategies. Pulmonary pathologies are one of the most common causes of death in human populations. Lung fibrosis, a phenomenon frequently associated with lung malfunction can be caused by many different conditions including ionizing radiation (radiotherapy), certain antibiotics (bleomycin), chronic inflammatory processes (sarcoidosis), environmental agents (asbestos, silica, certain gases), chronic conditions (rheumatoid arthritis), and mutations in certain genes (cystic fibrosis). The first of these conditions, radiation-induced pulmonary injury, is the major limiting factor for the successful treatment of non-small cell lung cancer – one of the most frequent and the most deadly cancer types in the world. Depending on the irradiated volume and the total radiation dose, approximately 5-55% of patients might develop clinically significant symptomatic pneumonitis and later fibrosis, which might be...

Research paper thumbnail of A novel culture system for the study of Alveolar type II cells proliferation and alveolar morphogenesis

Research paper thumbnail of Lung engraftment of fluorescent microspheres after hemithorax irradiation of mice, 60, Molecular concepts inepithelial differentiation, pathogenesis and repair

Research paper thumbnail of Equally reprogrammed human iPS cells from dermal fibroblasts proliferate differently

Research paper thumbnail of Genomic engineering of the cystic fibrosis gene in patient-derived iPS cells

Cystic Fibrosis is a hereditary disease produced by the absence or malfunctioning of the Cystic F... more Cystic Fibrosis is a hereditary disease produced by the absence or malfunctioning of the Cystic Fibrosis Transmembrane Conductase Regulator (CFTR) gene. To date over 1,200 alterations in the DNA composition of the CFTR gene have been detected, although the deletion of the phenylalanine in position 508 (DF508) is responsible for more than 70% of the cases described in the European Population. CF is a degenerative disease, which can be considered as the main genetic cause of death in Caucasian children. Its first manifestations occur in early childhood, generally affecting the respiratory tract, and later extending to other organs. The identification and isolation of the gene responsible for the disease raised great expectations of finding a treatment. However, such hopes have yet to be realized. Different attempts to develop effective gene therapy protocols have not provided satisfactory results. We have opted instead for a genomic engineering approach, in which homologous recombinat...

Research paper thumbnail of The organizer factors Chordin and Noggin are required for mouse forebrain development

Research paper thumbnail of Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis

International Journal of Pharmaceutics, 2014

Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudom... more Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200-400 nm size, high drug entrapment (79-94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys. 2014 Elsevier B.V. All rights reserved.

Research paper thumbnail of Nanoparticule lipidique de pol ymyxine

The present invention is related to a lipid nanoparticle comprising at least one antibiotic from ... more The present invention is related to a lipid nanoparticle comprising at least one antibiotic from the polymyxin family, a lipid fraction and one or more surfactants. The invention is also related to the use of the nanoparticle in the prevention and/or treatment of respiratory tree infectionsPeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)B1 Patente sin examen previ

Research paper thumbnail of Lipid nanoparticle of polymyxin

A lipid nanoparticle that includes at least one antibiotic from the polymyxin family, a lipid fra... more A lipid nanoparticle that includes at least one antibiotic from the polymyxin family, a lipid fraction, and one or more surfactants. The lipid nanoparticle is useful in the prevention and/or treatment of respiratory tree infectionsPeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Research paper thumbnail of 834 Correspondence

in red color overlaying a grayscale light image of the whole mouse (A-C), 10- m m sections of par... more in red color overlaying a grayscale light image of the whole mouse (A-C), 10- m m sections of parenchy-mal organs (D). Scale bars correspondent to 1 cm (A-C) and 20 m m (D). Analyses of time dynamics of iPS distribution through the paren-chymal organs might allow for the quantifi cation of their relative homing capabilities in the organ of interest and, thereby, better clarifi cation of their role in the different pathologic processes.

Research paper thumbnail of Patterning by genes expressed in Spemann's organizer

Cold Spring Harbor symposia on quantitative biology, 1997

... EM DE ROBERTIS, S. KIM, L. LEYNS, S. PICCOLO, D. BACHILLER, E. AGIUS, JA BELO, A. YAMAMOTO, A... more ... EM DE ROBERTIS, S. KIM, L. LEYNS, S. PICCOLO, D. BACHILLER, E. AGIUS, JA BELO, A. YAMAMOTO, A. HAINSKI-BROUSSEAU, B. BRIZUELA ... 1997; for review, see Bouwmeester and Leyns 1997), have led to the unex-pected realization that the vertebrate head may be in ...

Research paper thumbnail of Nanopartícula lipídica de polimixina

La presente invencion se relaciona con una nanoparticula lipidica que comprende al menos un antib... more La presente invencion se relaciona con una nanoparticula lipidica que comprende al menos un antibiotico de la familia de las polimixinas, una fraccion lipidica y uno o mas tensioactivos,y el uso de la nanoparticula en la prevencion y/o tratamiento de infecciones del arbol respiratorio.

Research paper thumbnail of Lipid nanoparticle of polymyxin

The invention relates to a lipid nanoparticle comprising at least one antibiotic from the polymyx... more The invention relates to a lipid nanoparticle comprising at least one antibiotic from the polymyxin family, a lipid fraction and one or more surfactants, and to the use of the nanoparticle in the prevention and/or treatment of infections in the respiratory system.

Research paper thumbnail of Molécula de ácido nucleico, proteína de fusión y método para modificar el material genético de una célula

La presente invencion se relaciona con una molecula de acido nucleico que codifica una proteina d... more La presente invencion se relaciona con una molecula de acido nucleico que codifica una proteina de fusion, comprendiendo la molecula de acido nucleico en sentido 5´---3´ de transcripcion al menos una secuencia de acido nucleico que codifica un dominio de union al ADN, y una secuencia de acido nucleico que codifica un dominio catalitico del tipo FokI, en donde en su extremo 3´comprende una secuencia de acido nucleico que codifica un peptido que comprende entre 18 y 23 aminoacidos, con una proteina de fusion obtenible por ejemplo de la transcripcion de dicha molecula, y con un metodo para modificar el material genetico de una celula mediante el uso de dicha molecula o proteina.

Research paper thumbnail of Chordin and noggin promote organizing centers of forebrain development in the mouse

Development, 2002

In this study we investigate the roles of the organizer factors chordin and noggin, which are ded... more In this study we investigate the roles of the organizer factors chordin and noggin, which are dedicated antagonists of the bone morphogenetic proteins(BMPs), in formation of the mammalian head. The mouse chordin and noggin genes(Chrd and Nog) are expressed in the organizer (the node) and its mesendodermal derivatives, including the prechordal plate, an organizing center for rostral development. They are also expressed at lower levels in and around the anterior neural ridge, another rostral organizing center. To elucidate roles of Chrd and Nog that are masked by the severe phenotype and early lethality of the double null, we have characterized embryos of the genotype Chrd-/-;Nog+/-. These animals display partially penetrant neonatal lethality, with defects restricted to the head. The variable phenotypes include cyclopia,holoprosencephaly, and rostral truncations of the brain and craniofacial skeleton. In situ hybridization reveals a loss of SHH expression and signaling by the prechor...

Research paper thumbnail of Safety and effectiveness of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) against P. aeruginosa: in vitro and in vivo studies following pulmonary and intramuscular administration

Nanomedicine: Nanotechnology, Biology and Medicine, 2019

Research paper thumbnail of Conservation of a functional hierarchy between mammalian and insect Hox/HOM genes

The EMBO Journal, 1994

3Corresponding author D.Bachiller and A.Macias have contributed equally to this work Communicated... more 3Corresponding author D.Bachiller and A.Macias have contributed equally to this work Communicated by G.Morata We have generated several transgenic Drosophila strains containing different mouse Hox genes under heat shock control and studied how their generalized expression affects Drosophila larval patterns. We find that they have spatially restricted effects which correlate with their genetic order and expression pattern in the mouse; as they are expressed more posteriorly in the mouse, they have more extensive effects in Drosophila. The generalized expressions of Hoxd-8 and d-9 modify Drosophila anterior head segment(s), but have no effect in the rest of the body. Hoxd-10 expression affects head and thorax, but not the abdomen. Finally, Hoxd-11 alters head, thorax and abdomen. The developmental effect of the Hox genes consists of a homeotic transformation of the affected segment(s), which exhibit a 'ground' pattern similar to that obtained in the absence of homeotic information, suggesting that Hox genes are able to inactivate Drosophila homeotic genes, but do not specify a pattern of their own. A partial exception is Hoxd-11 which, even though it has a general suppressing effect, can also activate the resident Abdominal-B and empty spiracles genes in ectopic positions. Our results strongly suggest a general conservation of the functional hierarchy of homeotic genes that correlates with genetic order and expression patterns.

Research paper thumbnail of Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis

International journal of pharmaceutics, Jan 10, 2016

Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most... more Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most prevalent. As a way to fight against this infection, nanotechnology has emerged over the last decades as a promising alternative to overcome resistance to antibiotics in infectious diseases. The goal of this work was to elaborate and characterize lipid nanoparticles for pulmonary delivery of tobramycin. Tobramycin-loaded nanostructured lipid carriers (Tb-NLCs) were prepared by hot melt homogenization technique. In addition, nanoparticles labeled with infrared dye (IR-NLCs) were used to investigate their in vivo performance after pulmonary administration. Tb-NLCs displayed a mean diameter size around 250nm, high drug encapsulation (93%) and sustained release profile. Tb-NLCs showed to be active against clinically isolated P. aeruginosa. Moreover, Tb-NLCs did not decrease cell viability and were able to overcome an artificial mucus barrier in the presence of mucolytics agents. During the ...

Research paper thumbnail of In vivo Langzeit-Evaluierung der Homing-Eigenschaften induzierter Stammzellen

Einführung Die Möglichkeit, somatische Zellen in induzierte pluripotente Stammzellen (iPS-Zellen)... more Einführung Die Möglichkeit, somatische Zellen in induzierte pluripotente Stammzellen (iPS-Zellen) umzuprogrammieren, eröffnet komplett neue Wege für die regenerative Medizin. Diese Zellen sind außergewöhnlich vielversprechend für die Reparatur von geschädigten Geweben und Organen (Sueblinvong and Weiss, 2010). Eine geeignete Zelltherapie eröffnet nun das große Potenzial, neue Behandlungsmethoden für eine Vielzahl von Erkrankungen wie Krebs zu entwickeln. Dabei ist der therapeutische Nutzen abhängig von der erfolgreichen Homing und Wiederbesiedlung von iPS-Zellen (Gonzalez, et al., 2011). In der Stammzellforschung wurden "Homing", als die Fähigkeit von Stammzellen beschrieben, zu ihrem Bestimmungsort oder zu ihrer "Nische" zu gelangen. Die ersten Transplantationen mit multipotenten Knochmarkszellen vor über 30 Jahren verdeutlichten die Tragweite eines effektiven Homings. In diesem Verfahren wurden gespendete Knochenmarkzellen, die ein neues Blut-produzierendes Sys...

Research paper thumbnail of Application of infrared protein to in vivo imaging of transplated cell migration

Research paper thumbnail of Stem cells based therapy for lung pathologies and blood circulation

There is a growing interest in the development of new Stem Cells (SCs) based therapeutic strategi... more There is a growing interest in the development of new Stem Cells (SCs) based therapeutic strategies. Pulmonary pathologies are one of the most common causes of death in human populations. Lung fibrosis, a phenomenon frequently associated with lung malfunction can be caused by many different conditions including ionizing radiation (radiotherapy), certain antibiotics (bleomycin), chronic inflammatory processes (sarcoidosis), environmental agents (asbestos, silica, certain gases), chronic conditions (rheumatoid arthritis), and mutations in certain genes (cystic fibrosis). The first of these conditions, radiation-induced pulmonary injury, is the major limiting factor for the successful treatment of non-small cell lung cancer – one of the most frequent and the most deadly cancer types in the world. Depending on the irradiated volume and the total radiation dose, approximately 5-55% of patients might develop clinically significant symptomatic pneumonitis and later fibrosis, which might be...

Research paper thumbnail of A novel culture system for the study of Alveolar type II cells proliferation and alveolar morphogenesis

Research paper thumbnail of Lung engraftment of fluorescent microspheres after hemithorax irradiation of mice, 60, Molecular concepts inepithelial differentiation, pathogenesis and repair

Research paper thumbnail of Equally reprogrammed human iPS cells from dermal fibroblasts proliferate differently

Research paper thumbnail of Genomic engineering of the cystic fibrosis gene in patient-derived iPS cells

Cystic Fibrosis is a hereditary disease produced by the absence or malfunctioning of the Cystic F... more Cystic Fibrosis is a hereditary disease produced by the absence or malfunctioning of the Cystic Fibrosis Transmembrane Conductase Regulator (CFTR) gene. To date over 1,200 alterations in the DNA composition of the CFTR gene have been detected, although the deletion of the phenylalanine in position 508 (DF508) is responsible for more than 70% of the cases described in the European Population. CF is a degenerative disease, which can be considered as the main genetic cause of death in Caucasian children. Its first manifestations occur in early childhood, generally affecting the respiratory tract, and later extending to other organs. The identification and isolation of the gene responsible for the disease raised great expectations of finding a treatment. However, such hopes have yet to be realized. Different attempts to develop effective gene therapy protocols have not provided satisfactory results. We have opted instead for a genomic engineering approach, in which homologous recombinat...

Research paper thumbnail of The organizer factors Chordin and Noggin are required for mouse forebrain development

Research paper thumbnail of Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis

International Journal of Pharmaceutics, 2014

Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudom... more Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200-400 nm size, high drug entrapment (79-94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys. 2014 Elsevier B.V. All rights reserved.