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News U10

News U10

Reversing pulmonary fibrosis has been achieved in murine models with peptide-loaded nanoparticles

A new study with participation of NANBIOSIS Unit 10 Drug Formulation unit of CIBER-BBN and UPV/EHU, has succeeded in preventing and reversing pulmonary fibrosis in experimental models with PLGA / PEI nanoparticles loaded with the GSE4 peptide. These results are the first step to study its possible antifibrotic effect in patients with idiopathic pulmonary fibrosis and other progressive fibrosing diffuse interstitial lung diseases that present altered telomere function.

NANBIOSIS unit 10 has been responsible for the design and manufacture of biodegradable nanoparticles loaded with the peptide.

The work is led by Rosario Perona and Leandro Sastre, researchers of CIBERER at the Biomedical Research Institute (CSIC/UAM), and Maria Molina-Molina, researcher at CIBERES and the Department of Pulmonology at the Bellvitge University Hospital. In addition, Guillermo Güenechea, from CIBERER at CIEMAT-IIS / FJD, and José Luis Pedraz, from CIBER-BBN and the University of the Basque Country have collaborated.

Idiopathic pulmonary fibrosis is a fatal fibrotic disease associated with aging with a median survival of 2 to 5 years. The disease usually appears around the age of 60, but there are familiar forms that can manifest at younger ages. Fibrosis appears as an aberrant healing response after alveolar damage and is characterized by the appearance of abnormal lung scarring, in which the restoration of epithelial integrity and tissue function is compromised. The mechanisms responsible for defective repair and regeneration are not well understood. However, recent studies suggest a possible role of accelerated aging and telomere shortening in the onset of the disease, mainly in familial forms.

The GSE4 peptide, of 11 amino acids, corresponds to an internal sequence of dyskerin, a protein that is part of the telomerase complex. GSE4 has protective effects on the cells of patients with the rare diseases dyskeratosis congenita and ataxia-telangiectasia, as it increases telomerase activity and cell growth and reduces DNA damage, oxidative stress and cell senescence.

The authors of the study, published in The FASEB Journal, used rat lung alveolar cells treated with a profibrotic agent, bleomycin, as a model. Expression of the GSE4 peptide or treatment with GSE4-PLGA / PEI nanoparticles causes a reversal of the inflammatory and fibrotic phenotype. There is an increase in telomerase activity, a decrease in DNA damage, and a decrease in inflammation and cell death. Furthermore, these cells show an inhibition in fibrosis.

In a rat model with bleomycin-induced pulmonary fibrosis, treatment with GSE4-PLGA / PEI nanoparticles has also increased telomerase activity and decreased DNA damage in alveolar cells. In both preventive and therapeutic protocols, GSE4-PLGA / PEI nanoparticles have prevented and attenuated lung damage and inhibited fibrosis. Histological analysis of the lungs of rats treated with bleomycin and GSE4-PLGA / PEI nanoparticles shows less fibrosis and inflammation and greater regeneration of the alveolar tissue, indicating the therapeutic efficacy of GSE4-loaded nanoparticles in this experimental pulmonary fibrosis model. .

This study supports the possibility of further investigating a potential curative treatment for patients with pulmonary fibrosis.

Reference article:

Pintado-Berninches, L., Montes-Worboys, A., Manguan-García, C., et al. “GSE4-loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage.” The FASEB Journal. 2021; 35: e21422. DOI: 10.1096/fj.202001160RR

(*) Explanation of the figure: Treatment with the profibrotic agent bleomycin decreases the number of cells that express the alveolar marker proSP-C (Bleo). Inoculation of GSE4-loaded nanoparticles into bleomycin-treated rats increases the number of cells expressing the marker, indicating alveolar regeneration.

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New Center for Research in Advanced Pharmaceutical Development

The NanoBioCel Research group, led by Jose Luis Pedraz, from CIBER-BBN and UPV/EHU, group that coordinates the Unit U10 Drug Formulation of NANBIOSIS -ICTS, together with the Provincial Council of Álava and the Center for Technological Research and Development TECNALIA, have launched last Thursday, January 21, the new Center for Research in Advanced Pharmaceutical Development, which will be located in the Lascaray Building, on the Álava campus of the UPV / EHU.

The objective of this center is to introduce new technologies in the pharmaceutical field and promote applied research in 3D Bio-printing, 3D Printing of medical devices and 3D Printing of new drugs.

This new center is a strategic and ambitious project, supported directly by the Provincial Council of Álava with a budget of € 2,500,000 that seeks to integrate the Álava region within the strategy proposed by the European Union in biosciences and technological development, sectors that have been boosted in the new investment initiative in response to the Coronavirus. This center is also a regional reference as a result of the leadership exercised by the NanoBioCel research group and a fruitful relationship of common projects to offer services to the pharmaceutical industry with Tecnalia2.

In the picture: Jose Luis Elejalde from Tecnalia, Javier Hernando from the Provincial Council of Alava, Pilar Garcia de Salazar, Lieutenant General Deputy and Provincial Deputy for Economic Development and Territorial Balance in the Provincial Council of Alava. Jose Luis Martin, Vice-Rector for Research of the UPV / EHU and Jose Luis Pedraz, IP NanoBioCel group.

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Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality

Researchers of CIBER-BBN Units of NANBIOSIS: U29 Oligonucleotide Synthesis Platform (OSP) at IQAC_CSIC, led by Prof. Ramón Eritja and U10 Drug Formulation, at UPV-EHU, led by Prof José Luis Pedraz, are coauthors of an article published by International Journal of Pharmaceutics.

Gene therapy strategies based on non-viral vectors are currently considered as a promising therapeutic option for the treatment of cystic fibrosis (CF), being liposomes the most commonly used gene carriers. Niosomes offer a powerful alternative to liposomes due to their higher stability and lower cytotoxicity, provided by their non-ionic surfactant and helper components. In this work, a three-formulation screening is performed, in terms of physicochemical and biological behavior, in CF patient derived airway epithelial cells. The most efficient niosome formulation reaches 28% of EGFP expressing live cells and follows caveolae-mediated endocytosis. Transfection with therapeutic cystic fibrosis transmembrane conductance regulator (CFTR) gene results in 5-fold increase of CFTR protein expression in transfected versus non-transfected cells, which leads to 1.5-fold increment of the chloride channel functionality. These findings highlight the relevance of niosome-based systems as an encouraging non-viral gene therapy platform with potential therapeutic benefits for CF.

The article acknowledges U10 Drug Formulation, for the intellectual and technical assistance

Article or reference:

Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality-Sainz-Ramos, M., Villate-Beitia, I., Gallego, I., A.L. Qtaish, N., Lopez-Mendez, T.B., Eritja, R., Grijalvo, S., Puras, G., Pedraz, J.L. International Journal of Pharmaceutics, 588, art. no. 119757, 2020. https://doi.org/10.1016/j.ijpharm.2020.119757

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Moore4Medical a project to accelerate innovation in electronic medical devices

The NanoBioCell group, led by Prof. Jose Luis Pedraz, participates in the European project Moore4medical. A project to accelerate innovation in emergencing medical devices with open tecnhology platforms. The NanoBiocel group, will focus on the lyophilization process of biopharmaceuticals and their use in microfluidic devices

The NanoBiocel research group of the University of the Basque Country / Euskal Herriko Unibertsitatea, which is part of the CIBER BBN and the ICTS Nanbiosis through the U10 Drug Formulation Unit, and led by Professor Jose Luis Pedraz of the Faculty of Pharmacy, participates in the European project Moore4medical, which aims to accelerate innovation in electronic and microfabricated devices for several emerging medical specialties. Specifically, the work of the NanoBiocel group will focus on optimizing the lyophilization process of biopharmaceuticals in microfluidic devices.
The three-year Moore4Medical project is funded by the public-private partnership ECSEL (Electronic Components and Systems for European Leadership), which manages a research and innovation program to strengthen the electronic components and systems sector to maintain to the European Union at the forefront of technological development. The total financing of the project amounts to € 68M, of which more than half a million have been awarded to the work of NanoBiocel.
In Moore4Medical, 68 partners participate (between private companies, universities and research institutions) from 13 countries and is led by the Dutch multinational Philips in its electronics and medical systems and service innovation divisions.

Microfluidic device
The NanoBioCell group will work, together with the Mondragón company microLIQUID, in the development of technology for integrating lyophilized drugs and their rehydration in a microfluidic device for their correct administration. The lyophilized drug will be integrated into the microfluidic device using specific techniques to ensure a good interaction between the fluid and the drug for delivery by the pump. The final objective is to design a system for the administration of drugs by parenteral route that is much more comfortable for patients and that improves the therapeutic compliance of treatments.
The microLIQUID company is a leading biotechnology company in the microfluidic technologies sector and will be in charge of the design and development of microfluidic modules.
In this work called ‘Drug Adherence’, integrated within the total project, the NanoBioCel group will team up with the Irish national institute Tyndall, the multinational pharmaceutical company AbbVie, the Fraunhofer Institute of Germany, the service innovation section of Philips, the company German Gaudlitz GmbH, specialist in polymers, the Karlsruhe Technological Institute in Germany and the HI Iberia company in Madrid.

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Ainhoa González Pujana, NANBIOSIS U10, 2019 best doctoral thesis award by the Bioaraba Research Health Institute

The Bioaraba Health Research Institute has awarded Ainhoa ​​González Pujana, a researcher at NanoBioCell and the Nanbiosis Platform through the U10 Drug Formulation (from CIBER-BBN and UPV-EHU), the award for the best doctoral thesis 2019 at the XXI Bioaraba Research and Innovation Conference, held last November 5 in Vitoria-Gasteiz.

Along with the recognition, the award consists of an economic endowment of € 1,000 in funds for R + D + i. The thesis, directed by Professor Rosa María Hernández and Dr. Edorta Santos Vizcaíno, has been carried out in the NanoBioCel group of the Faculty of Pharmacy of the University of the Basque Country (UPV / EHU). Under the title “Bioinspired three-dimensional multifunctional systems to enhance the therapeutic potential of mesenchymal stromal cells”, the thesis has focused on the design of biomimetic matrices that enhance the immunomodulatory effect of mesenchymal stem cells, as a therapeutic alternative for treatment of the immunological alterations that occur in diseases such as ulcerative colitis, Crohn’s disease or Lupus erythematosus.

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How to delay vision loss in hereditary retinal dystrophies? Looking for the most effective and economical pharmacological nanotherapy

Researchers from the CIBER-BBN and NANBIOSIS are participating in a new project that aims to achieve the most effective, specific and economical pharmacological nanotherapy that allows delaying the death of retinal cells and subsequent loss of vision in hereditary retinal dystrophy. retinitis pigmentosa, regardless of the genetic defect causing the disease.

In this project, coordinated by the researcher Regina Rodrigo, the ONCE and the Prince Felipe Research Center (CIPF) of Valencia collaborate, together with researchers from the CIBER of Rare Diseases (CIBERER) and the Manises Hospital in Valencia. On behalf of the CIBER-BBN, the scientific director, Ramón Martínez Máñez, together with Elena Aznar from the IDM-UPV group of the Polytechnic University of València, José Luís Pedraz, Gustavo Puras and Idoia Gallego, from the group of the University of the Basque Country and Nanbiosis.

The NANBIOSIS participation in the project will be through the U10 Drug Formulation unit (from @CIBERBBN and @upvehu), led by NanoBioCell Group and Prof. José Luis Pedraz and U26 NMR: Biomedical Applications II , led by IDM-UPV-UV Group, led by Prof. Ramón Martínez Máñez. Elena Aznar, researcher of CIBER-BBN at IDM-UPV-UV explained “We use the unit to characterize the nanoparticles. Through a solid phase NMR confirms that the molecular gate has been correctly attached to the surface of the nanoparticles“.

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision. Although it is considered a rare disease, it is the leading genetic cause of blindness in developed countries. So far there is no effective treatment, although there are various therapeutic approaches such as gene therapy, cell therapy, pharmacological therapy, optogenetics or electronic implants.

During the progression of the disease, an important inflammatory component has been observed that may contribute to its pathogenesis. In this sense, different anti-inflammatory strategies have been evaluated. The research group has successfully tested one of these strategies in preclinical models of retinitis pigmentosa. However, the implementation of this therapeutic strategy with nanocarriers as controlled release delivery systems would improve the mode of action of the administered drug, avoiding its degradation, increasing its half-life, stability or its availability in the retina. In this project, two types of nanocarriers will be used and their effect on the degenerative process in a murine model of retinitis pigmentosa will be evaluated.

  • PICTURE: Hematoxylin and eosin image showing that intravitreal blockade of the cytokine TNFα with Adalimumab-type monoclonal antibodies (ADA) reduces retinal degeneration, preventing the death of photoreceptors (RF) in the murine model of retinitis pigmentosa, rd10 mouse.
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Laura Saenz del Burgo, NANBIOSIS U10, award for the best emerging researcher at the XXI Bioaraba Research and Innovation Conference

The CIBER-BBN researcher at the University of the Basque Country (UPV-EHU), Laura Saenz del Burgo, received, within the framework of the XXI Bioaraba Research and Innovation Conference, the award for the “Best Emerging Researcher 2020”.

The researcher of the NanoBioCel group of the UPV / EHU, who belongs to the CIBER BBN and the U10 Drug Formulation of the ICTS of Nanbiosis, is an active part within the research group led by Jose Luis Pedraz and focuses her work in the areas of Regenerative Medicine , Tissue Engineering and 3D-Bioprinting.

The conference was held at the Palacio de Congresos de Europa, in Vitoria (Álava) last Thursday, November 5. It is a meeting forum between research staff, both from the health system and the university, the company, technology centers, institutions and citizens.

The Bioaraba Research and Innovation Awards want to recognize and encourage people and institutions whose dedication directly affects the improvement of the health and quality of life of the population, through not only purely scientific or healthcare work, but also from a contribution adequate social.

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Regenerating ankle joints with collagen- and gelatine-based implants

 TRIANKLE is an EU Project to develop regenerative therapies for ankel injuries in which participate NanoBioCell Group and NANBIOSIS U10 Drug Formulation unit (from CIBER-BBN and UPV/EHU), led by José Luis Pedraz.
 The main objective is to reduce the time of recovery down to 50% and
increase the functionality ratios up to 10-15%.
 Research consortium is composed of 12 partners from 5 European countries and counts with a EU funding of €5.9M.
 It is expected that the results of the project will be very well received by potential patients, such as elite athletes and patients with osteoarthritis, through the outreach work of the FCB Barça Innovation Hub and the OAFI, both members of the consortium
.

On November 6th, the grant agreement No: 952981 funded by the European
Commission (Horizon 2020 Program) by which the TRIANKLE project comes into operation was signed. The TRIANKLE consortium – made up of 12 European organisations, will develop 3D bioprinted personalised scaffolds for tissue regeneration of ankle joints. This ambitious research project in regenerative medicine comes with an overall budget of €5.9M and
will be developed over 4 years, starting January 2021. The consortium aims to create innovative personalised collagen- and gelatine-based implants manufactured with 3D technology for patients with tendinopathies such as Achilles tendon partial ruptures and cartilage injuries.

Tendinopathies and osteoarthritis (OA) are extremely common and expensive, especially among the elderly, women and professional athletes. In addition to quality of life, both conditions substantially impact healthcare systems of economies worldwide (OA costs €76.5 billion in EU every year, while tendinopathies have an estimated worldwide expenditure above €140,000 million).

Horizon 2020 is the biggest EU Research and Innovation programme ever with nearly €80 billion of funding available over 7 years (2014 to 2020) – in addition to the private investment that this money will attract. It promises more breakthroughs, discoveries and world-firsts by taking great ideas from the lab to the market.

For more info: http://ec.europa.eu/programmes/horizon2020/en/what-horizon-2020

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From natural by-products to cell delivery systems for regenerative medicine

Researchers from NANBIOSIS U10 Drug Formulation unit (CIBERBBN – UPV/EHU led Rosa María Hernández, have developed a biomedical device consisting of by-products from the food industry and which displays excellent properties for use in regenerative medicine. The work has been published in the Green Chemistry Jurnal, one of the most prestigious international journals in chemistry and the second most important one in the field of sustainable science. The work has also been selected for the cover page of this issue.

Researchers in the UPV/EHU’s NanoBioCel and Biomat groups have developed a biomedical device consisting of by-products from the food industry and which displays excellent properties for use in regenerative medicine. The novel device comprises soy protein and chitin, which form a matrix with a porous, interconnected microarchitecture similar to that of certain body tissues.

Added to the growing need in recent years to develop new therapies for biomedical applications is the widely called-for social requirement to be environmentally friendly. In this respect, the group of researchers has shown that natural by-products from the food industry, normally discarded in industrial processes, could be an excellent source of biomaterials for producing biomedical devices.

“It is important to point out that to date no one has exploited the potential in regenerative medicine displayed by soy protein and chitin blended in a microporous matrix,” stressed the researchers. “As the first milestone in this respect, this novel device incorporates two natural components obtained from the food industry, thus contributing towards the widely called-for social requirement to upgrade waste from production on an industrial level. The device has also displayed some physico-chemical and mechanical properties suitable for applications in regenerative medicine. What is more, it has also been found to be totally biocompatible not only in in vitro cell lines but also in an in vivo murine model.  Finally, we have confirmed that this device is capable of hosting a large number of viable stem cells inside it, thus increasing its level of bioactive compound secretion and displaying its potential as a very effective vehicle in cell therapy.”

This biotechnological approach may have a potentially successful application in the matrix-based regenerative medicine industry. These devices capable of hosting stem cells are destined to be the revolution, not only in biomedical research but also in everyday clinical practice. “Clinical scenarios as complex as chronic injuries or bone problems need a multifocal approach which combines bioactive matrices with biological agents having regenerative effects,” they concluded.

Article of reference

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NANBIOSIS researchers featured in the 15th Edition of Spanish Researchers Ranking

The 15th edition of the Webometrics Ranking of World Universities has been published, ranking researchers in Spain as well as Spaniards doing research abroad. A total of 11 Directors of NANBIOSIS units appear on the most recent list, featured on the top 2000. The list is ordered by the h-index, a metric that calculates research impact based on a correlation of papers published and number of citations, and then by number of citations. The result is a list of whose’s publications have had more impact online.

NANBIOSIS researchers featured are Fernando Albericio (#207), scientific director of U3 Synthesis of Peptides Unit, Ramón Martínez Máñez (#342) U26 NMR: Biomedical Applications II, Jaume Veciana (#459) U6 Biomaterial Processing and Nanostructuring Unit, José Luis Pedraz (#906) U10 Drug Formulation unit, Jesús Santamaría (#912) U9 Synthesis of Nanoparticles Unit, Ramón Eritja (#1022) U29 Oligonucleotide Synthesis Platform (OSP), Pablo Laguna (#1153) U27 High Performance Computing, Antoni Villaverde (#1249) U1 Protein Production Platform (PPP), Laura Lechuga (#1511) U4 Biodeposition and Biodetection Unit M.Pilar Marco (#1517), U2 Custom Antibody Service (CAbS), and Josep Samitier (#1836) U7 Nanotechnology Unit.

This list reflects on the impact online publication can have as a tool to share knowledge. 

For further information: here

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