NANBIOSIS, U20. In Vivo Experimental Platform, led by Dr. Ibane Ibasolo, has been updated and improved as a result of its participation in the project FICTS1420-20, selected by the MICINN for co-financing by the FEDER Program in ICTS 2014-2020 (Equipment for setting standardized immunotoxicology assays for the U20 -NANBIOSIS I17 Action of the Investment Plan-)
In the picture: microencapsulated cardiospheres 10X Captured Brightfield with DM_RGB_Brightfield with DM
The European project POSITION-II has been selected for publication in the ‘Results in Brief’ section of the Community Research and Development Information Service (CORDIS) website. CORDIS is the European Commission’s primary source of results from the projects funded by the EU’s framework programmes for research and innovation (FP1 to Horizon 2020).
The resulting short article has now been published on the CORDIS website in six languages.
The European project POSITION II “A pilot line for the next generation of smart catheters and implants” is an alliance of European leaders, united to improve technology and offer cheaper, easier to use, more efficient and technologically advanced catheters by incorporating sensors and real-time positioning and monitoring systems. This new generation of catheters will improve the treatment of multiple pathologies, through new therapeutic tools such as cell therapy and tissue engineering implemented in the project by the U10 Drug Formulation of the ICTS Nanbiosis, which is integrated in the NanoBioCel group of CIBER-BBN and UPV/EHU.
The following actions have been carried out in NANBIOSIS U10 Drug Formulation during the execution of the project:
– Isolate, expand and characterize cardiosphere-derived cells (CDCs). CDCs were isolated from porcine cardiac tissue, and their release profile of immunomodulatory factors was determined.
– To optimize the encapsulation conditions of CDCs in alginate microcapsules.
– Evaluate whether the physical and chemical properties of the encapsulated CDCs were suitable for the catheter developed in the project.
– Determine that the secretion profile of trophic factors did not change in CDCs after encapsulation.
– Provide the TME Lab group and NANBIOSIS U13 of CIBER-BBN and the University of Zaragoza with the microcapsules and encapsulated CDCs required for their mechanical characterization and to evaluate the behavior of the capsules in the catheter and in the animals at the NANBIOSIS units of Center for Minimally Invasive Surgery in Extremadura (CCMIJU). Other collaborations during the execution of the project were established with the Fraunhofer EMFT group in Germany and with the Spanish company IberHospitex, manufacturer of the catheters.
Other related news:
Pancreatic ductal adenocarcinoma is a highly devastating orphan disease with poor prognosis even when diagnosed early (The survival rate after 5 years (< 5%) has not changed over the last 30 years, despite tremendous research efforts) The european project NoCanTher, in wich participates NANBIOSIS U20 of (VHIR and CIBER-BBN) is a nanotechnology-based approach aimed to scale-up under GMP conditions and evaluate a nanoformulation for a combined therapy with chemotherapy against this pancreatic cancer.
The international clinical study, carried out in the framework of the project is now incorporating the first pacient in Spain with this type of nanotherapy.
The clinical study is based on the results obtained in the preclinical phase of the NoCanTher project, with the group of the CIBBIM (of CIBER-BBN and VHIR, led by Dr. Ibane Abasolo). This new technology based on magnetic nanoparticles increases the accessibility of chemotherapy to pancreatic tumors. Researchers have developed magnetic iron nanoparticles that, under an alternating magnetic field, generate heat – magnetic hyperthermia. This heat is able to be used because the tumor cells are still more sensitive to the standard treatment with chemotherapy and, therefore, in greater efficiency, and ultimately it is possible to directly destroy these cells.
As explained by Dra. Ibane Abasolo, Scientific Director of Nanbiosis unit 20 of CIBER-BBN and VHIR: “NANBIOSIS has played an important role in this project in relation with the preclinical in vivo trials in animal models (mice). We made human pancreatic cancer cells grow and studied the efficacy of nanoparticles and their combination with chemotherapy. Specifically, we saw that i) tumor heating by magnetic hyperthermia slowed down tumor growth, but that it was necessary to combine this treatment with conventional chemotherapy to have a better effect, that ii) the hyperthermia-chemotherapy sequence that worked best (it is better to warm up first and treat with chemotherapy later than to put chemotherapy first) and iii) that the combination of hyperthermia/chemotherapy was beneficial because it greatly reduces the stroma of the tumor and makes it easier for chemotherapy to reach tumor“.
The NoCanTher project is coordinated by IMDEA Nanociencia (Madrid) and includes the participation of eleven national and international centers: BioKeralty Research Institute (Miñano), ImmuPharma (London), Chemicell (Berlin), University Hospital (Jena, Germany), Resonant Circuits (London), Vall d’Hebron Research Institute (VHIR) (Barcelona), Vall d’Hebron Institut d’Oncology (VHIO) (Barcelona), Trinity College (Dublin), Paris Diderot University (Paris), Hospital Universitari of Fuenlabrada (Madrid). The initiative is funded by Horizon 2020 (GA:685795).
A CIBER-BBN team at the University of Zaragoza has developed intelligent shuttles (cell vesicles -exosomes-) to transfer nanoparticles to the interior of tumor cells and destroy them by means of heat and without drugs, following the “Trojan horse” strategy.
“NANBIOSIS U9, “Synthesis of Nanoparticles Unit has developed the procedure to be able to internalize gold nanoparticles, with surface plasmon in the NIR electromagnetic range, inside extracellular vesicles derived from stem cells. The synthesis of the gold nanoparticles has been produced according to the synthesis procedures of UNIT 9 of the ICTS NANBIOSIS based on the galvanic substitution reaction in the liquid phase of Co atoms by Au+3 ions, generating a hollow structure whose geometry gives gold nanoparticles unique optical properties that allow the absorption of NIR light and its conversion into heat” , explain the researchers of NANBOSIS U9 Pilar Martín-Duque, Victor Sebastián and Jesús Santamaría.
They are gold nanoparticles belonging to what is known as “plasmonic nanoparticles” that have the ability to heat up when receiving near-infrared radiation, which penetrates the body. It is, therefore, a treatment without drugs, which uses the heat generated by the particles to cause cell death around them. These particles are taken to the tumor by exosomes, having been proved efectived in animal models.
“We have managed to reduce or eliminate tumors in mice without drugs, only with the heat generated by irradiating them with a laser. In other words, we inject the exosomes with the nanoparticles into the tail of the mouse and they alone “search” for the tumor, not only in conventional models but also in multinodular ones, similar to metastatic processes”, explains Pilar Martín Duque.
For futher information:
Article of reference:
Transfer of photothermal nanoparticles using stem cell derived small extracellular vesicles for in vivo treatment of primary and multinodular tumors. María Sancho-Albero, Miguel Encinas-Giménez, Víctor Sebastián, Estela Pérez, Lluis Luján, Jesús Santamaría, Pilar Martín-Duque Journal of Extracellular Vesicles 2022 https://onlinelibrary.wiley.com/doi/full/10.1002/jev2.12193
Start-ups / SMEs! Are you working on innovative medical products using nanotechnology? This is your call for development and marketing solutions!
Last week took place the SAFE-N-MEDTECH Open Call on line info session with the idea to present the open call with a bit more detail. A few presentations and specially a time for questions and answers were organized by Anaïs Le Corber, Network Manager of CEBERG, the council of European Bioregions, partner of the project.
The webinar was recorded and it is available here:
First of all, Angel del Pozo, Coordinator of the SAFE-N-MEDTECH, gave an insight of the project.
Then, Miguel Duarte from IMM (Portugal), the business development partner of the project, presented the services offered
After him, Qwentin Pankhurst, chairman of Resonant Circuits Ltd. explained his experience as user, having a tase case in the project.
Finaly, before the space for questions and answers, Ibane Abasolo, Scientific Director of NANBIOSIS U20, from CIBER-BBN and Vall D’Hebron Institute Research in Barcelona, presented with more detail the clinical validation services available in this open call.
SAFE-N-MEDTECH OITB Safety testing in the life cycle of nanotechnology-enabled medical technologies for health is a H2020 project with the objective of providing services and support to companies and other organizations for accelerating the development and commercialization of innovative MedTech solutions based on nano-enabled technology.
How can this call suit you?
Qwentin Pankhurst explained his experience: “As a medtech start-up we do not have the external experience to cover all the safety related aspects of product development for MDR compliance, we needed clear uncomplicated advance and solutions, ideally we needed a “one-stop-shop”…
“Even if a client accesses only a part of the offering, the fact that the OITB is seeking to cover the entire pathway from design input to clinical testing is important as it underpins a connected-thinking approach.”
Submission deadline: March 21st 2022, 23:59 CET
The time line: It is espected that the evaluation process will take around one month. Then NDAs will be signed before starting the work, which could be carried during one year approximatly.
The technology assesment area of the SAFE-N-MEDTECH OITB well carry out a first examitanion toguether with the applicant of the available data, the quality of the data, the needs of the product an other relevant aspects. A technology assitant proposal will ve developed and the services needed will be defined toguether with the client.
Call documents:
This call uses funds obtained within the scope of the SAFE-N-MEDTECH project funded by European Union´s Horizon 2020 Research and Innovation Program. (Grant Agreement No. 814607)
Esther Pueyo, member of the BSICoS group, which coordinates NANBIOSIS U27 “High Performance Computing” from CIBER-BBN and I3A-UZ, participes with Lina Badimon, professor at the CSIC and group leader at the CIBERCV in the first of a series of videos where two women scientists share their experiences, prepared by the Scientific Culture and Innovation Unit (UCC+i) of the CIBER
Both researchers work in the field of Cardiology and share their passion for science and their vocation to help patients. In this video they talk in depth about their career, their difficulties, their achievements, and what their vision is about the future of women in Science and Cardiology..
“The message to university students is that they can change the future: this is what is known but you can contribute to the knowledge”`, points out Lina Badimon, who is in charge of Women in Cardiology at the European Society of Cardiology. “Women are the majority in the first stages of the scientific career but, then, women do not advance at the speed that men do and this is the point difficult to overcome for women” states Esther Pueyo.
WHY DO CELEBRATE TODAY THE INTERNATIONAL #RareDiseaseDay?
29 of February is a ‘rare’ date and February, a month with a ‘rare’ number of days, has become a month to raise awareness about rare diseases and their impact on patients’ lives. Since 2008 thousands of events happen every year all around the world and around the last day of February with the aim of improving equity and reducing stigmatization for people who live with more than 6,000 rare diseases.
WHAT ARE RARE DISEASES
Rare diseases are pathologies or disorders that affect a small part of the population (less than 5 per 10,000 inhabitants) and generally have a genetic component. They are also known as orphan diseases.
Diseases present a series of particular symptoms, and it is very difficult to diagnose what their true cause is. These disorders or alterations that patients present must be evaluated by a specialist, depending on each case.
Today 5% of the world population suffer from them. This translated into numbers, corresponds to approximately 300 million affected.
A patient with a rare disease waits an average of 4 years to obtain a diagnosis, in 20% of cases it takes 10 or more years to achieve the proper diagnosis.
ORPHAN DRUGS
To combat this disease, patients need to be treated with so-called orphan drugs. They serve to prevent and treat pathology. Its composition is based on biotechnological compounds whose manufacture is very expensive and not profitable for companies. For this reason, cooperation of governments is needed as well as financial incentives to encourage pharmaceutical companies to develop and market medicines to make these treatments accessible to a greater number of people.
FABRY DISEASE
Fabry is one of the rare diseases that currently lack a definitive cure. Symptoms may include episodes of pain, especially in the hands and feet (acroparesthesias); small dark red spots on the skin called angiokeratomas; decreased secretion of sweat (hypohidrosis); opacity of the cornea (cataracts) and hearing loss. Internal organs such as the kidney, heart, or brain may be involved, resulting in progressive kidney damage, heart attacks, and strokes.
Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients.
“SMART 4 FABRY” EUROPEAN PROJECT
CIBER-BBN, through the researcher Nora Ventosa has coordinated the european project “Smart-4-Fabry” developed during 2017-2021, the proyect was undertaken by a consortium formed by ten partners, including private companies and public institutions in Europe and Israel, with a Horizon 2020 financial programme by the European Commission (H2020-NMBP-2016-2017; call for nanotechnologies, advanced materials, biotechnology and production; Proposal number: 720942-2).
In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability.
Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease.
Through a risk analysis and a Design of Experiments (DoE), researechers obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.
The new nanoformulation developed by Smart4Fabry for the treatment of Fabry disease achieved the ODD (Orphan Drug Designation) by the European Commission. The new nanomedicine is more effective and has a better biodistribution than the current treatments, based on enzyme replacement. The new nanomedicine is based on a nanovesicle that protects the enzyme and achieves a better cell internalisation, thus reducing the doses needed, the total cost and improving the quality of patients.
Four units of NANBIOSIS participated in the project:
– U1 Protein Production Platform (PPP) led by Neus Ferrer and Antony Villaverde at IBB-UAB for the production and purification in different expression systems for R&D purposes.
– U3 Synthesis of Peptides Unit led by Miriam Royo at IQAC-CSIC performed all the chemical process of the Smart-4-Fabry project, i.e. design and synthesis of peptides used as targeting ligands in the nanoliposome formulation.
– U6 Biomaterial Processing and Nanostructuring Unit led by Nora Ventosa at ICMAB-CSIC developed tasks related to the manufacture of the nanoliposome formulation of GLA enzyme and the physico-chemical characterization (this unit counts with plants at different scales, from mL to L, which allow process development by QbD and process scale-up, as well as instrumental techniques for assessment of particle size distribution, particle concentration, particle morphology and stability, and Z-potential) .
– U20 In Vivo Experimental Platform led by Ibane Abásolo at VHIR carried out the non-GLP preclinical assays of the project (in vivo efficacy, biodistribution and tolerance/toxicity assays).
PHOENIX: OPEN INNOVATION TEST BED
Researchers of CIBER-BBN and NANBIOSIS, led by Nora Ventosa, are currently participating in another european project, PHOENIX “Enabling Nano-pharmaceutical Innovative Products” in the framework of which this novel nanomedicine developed under the Smar4Fabry project and designed as Orphan Drug by the EMA, will be scaled-up and manufactured under GMP to enable its clinical testing.
Articles of reference:
Josep Merlo-Mas, Judit Tomsen-Melero, José-Luis Corchero, Elisabet González-Mira, Albert Font, Jannik N. Pedersen, Natalia García-Aranda, Edgar Cristóbal-Lecina, Marta Alcaina-Hernando, Rosa Mendoza, Elena Garcia-Fruitós, Teresa Lizarraga, Susanne Resch, Christa Schimpel, Andreas Falk, Daniel Pulido, Miriam Royo, Simó Schwartz, Ibane Abasolo, Jan Skov Pedersen, Dganit Danino, Andreu Soldevila, Jaume Veciana, Santi Sala, Nora Ventosa, Alba Córdoba, “Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method”, The Journal of Supercritical Fluids, Volume 173, 2021, 105204, https://doi.org/10.1016/j.supflu.2021.105204.
Judit Tomsen-Melero, Solène Passemard, Natalia García-Aranda, Zamira Vanessa Díaz-Riascos, Ramon González-Rioja, Jannik Nedergaard Pedersen, Jeppe Lyngsø, Josep Merlo-Mas, Edgar Cristóbal-Lecina, José Luis Corchero, Daniel Pulido, Patricia Cámara-Sánchez, Irina Portnaya, Inbal Ionita, Simó Schwartz, Jaume Veciana, Santi Sala, Miriam Royo, Alba Córdoba, Dganit Danino, Jan Skov Pedersen, Elisabet González-Mira, Ibane Abasolo, and Nora Ventosa. Impact of Chemical Composition on the Nanostructure and Biological Activity of α-Galactosidase-Loaded Nanovesicles for Fabry Disease Treatment, ACS Appl. Mater. Interfaces 2021, 13, 7, 7825–7838 ( https://doi.org/10.1021/acsami.0c16871).
An Open Call within H2020 project SAFE-N-MEDTECH OITB -Safety testing in the life cycle of nanotechnology-enabled medical technologies for health– has been launched with the objective of providing services and support to companies and other organizations with the aim of accelerating the development and commercialization of innovative MedTech solutions based on nano-enabled technology.
SAFE-N-MEDTECH in which CIBER-BBN is a partner througth its ICTS NANBIOSIS, gathers expertise from 28 partners around the world focused in enabling the safe translation of nano-enabled medical technologies from Proof of Concept to markets and clinical practice funded project
SAFE-N-MEDTECH with its key expertise and extensive knowledge in nano-enabled medical technologies, offers characterization, pre-clinical validation, access to biobanks and patient samples, scale up and regulatory support, technology assessment and horizon scanning.
Submission deadline: March 21st 2022, 23:59 CET
CALL DOCUMENTS – HOW TO APPLY:
EXAMPLES OF SUPPORT SERVICES:
Nanoparticle Characterisation
Pre-Clinical Development
In Silico
Clinical Validation
Assistance in prototyping and qualification of manufacturing facilities
Business development coaching, links with business angels, investors, capital risk, etc
Regulatory Assessment
Health Technology Assessment
This call uses funds obtained within the scope of the SAFE-N-MEDTECH project funded by European Union´s Horizon 2020 Research and Innovation Program. (Grant Agreement No. 814607)
Obesity is caused by the enlargement of the white adipose tissue (WAT) depots, characterized by the hypertrophic enlargement of malfunctioning adipocytes within WAT, which increases the storage of triglycerides (TG) in the lipid droplets (LD). Adipogenesis pathways as well as the expression and activity of some extracellular matrix receptors integrins are upregulated. Integrinβ1 (INTB1) is the main isoform involved in WAT remodeling during obesity and insulin resistance-related diseases. We recently described Integrin Linked Kinase (ILK), a scafold protein recruited by INTB1, as an important mediator of WAT remodeling and insulin resistance. As the few approved drugs to fight obesity have brought long-term cardiovascular side effects and given that the consideration of INTB1 and/or ILK modulation as anti-obesogenic strategies remains unexplored, we aimed to evaluate the anti-obesogenic capacity of the clinically approved anticoagulant Tirofiban (TF), stated in preclinical studies as a cardiovascular protector.
TF reduces the levels of F‑actin in adipocytes. Deprived differentiated adipocytes from c3H10T1/2 were treated with TF 50 µM or vehicle (CT) or co‑treated with specific INTB1 blocking antibody (HMB1) for the indicated times.
In the picture: Confocal images of F-actin dyed with phalloidin (red) and nuclei with DAPI (blue) of differentiated adipocytes treated with Tirofiban or vehicle (CT), where previously Integrin-beta1 was blocked with a specific blocking antibody (HMB1) for the indicated times. Scale bars 50 μm.
F-actin confocal images were determined by the Confocal Microscopy Service of the ICTS ‘NANBIOSIS’ U17, of the Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) with the technical assistance of Isabel Trabado, and pharmacokinetics were determined in the Applied Chemistry and Biotechnology Center (CQAB), both at Universidad de Alcalá.
Article of Reference:
de Frutos S, Griera M, Hatem-Vaquero M, Campillo S, Gutiérrez-Calabres E, García-Ayuso D, Pardo M, Calleros L, Rodríguez-Puyol M, Rodríguez-Puyol D. The integrin beta1 modulator Tirofiban prevents adipogenesis and obesity by the overexpression of integrin-linked kinase: a pre-clinical approach in vitro and in vivo. Cell Biosci. 2022 Jan 28;12(1):10. doi: 10.1186/s13578-022-00746-1. PMID: 35090553.
The leader of the NanoBioCell Group form CIBER-BBN and UPV/EHU, Jose Luis Pedraz, and the reaearches Laura Saenz del Burgo and Markel Lafuente have received the 2021 Award from the Academy of Pharmacy of Castilla y León, on February 4, at the city of Salamanca, for the work entitled: “Design and Characterization of a biotin formulated with nanocellulose, alginate and Gags for use in 3D bioprinting and application in cartilage regeneration“, the content of this research work has been published in the Journal Macromolecular Science under the title: “Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage Regeneration” The pharmacotechnical and rheological characterization work of the designed bioinks has been carried out in the U10 Drug Formulation of the Nanbiosis ICTS of the Faculty of Pharmacy of the University of the Basque Country and CIBER-BBN.
In addition, Prof. Jose Luis Pedraz has been appointed Corresponding Academician at the Academy of Pharmacy of Castilla y León.
Also the researcher of the NanoBiocel group, Professor Edorta Santos Vizcaíno, belonging to the CIBER BBN and the U10 Drug Formulation of the Nanbiosis ICTS, and María Gil Atienza, have been recognized that same day, with a second prize by the Academy of Pharmacy of Castilla y León for the research work: “Use of extracellular vesicles to transport antitumor agents in the treatment of cancer”. This work was carried out in the Laboratory of Pharmacy and Pharmaceutical Technology of the University of the Basque Country.
