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Design of parenteral MNP-loaded PLGA nanoparticles by a low-energy emulsification approach as theragnostic platforms for intravenous or intratumoral administration

Encapsulation of magnetic nanoparticles (MNP) into PLGA nanoparticles has been achieved by nano-emulsion templating using for the first time both, a low-energy emulsification method as well as biocompatible components accepted for pharmaceuticals intended for human use. The incorporation of MNP by nano-emulsion templating method proposed in this work has been investigated in two different systems applying mild process conditions and is shown to be simple and versatile, providing stable MNP-loaded PLGA nanoparticles with tunable size and MNP concentration. MNP-loaded PLGA nanoparticles showed sizes below 200 nm by DLS and 50 nm by TEM, and mean MNP loading per PLGA nanoparticle of 1 to 4, depending on the nanoparticle dispersion composition. Physical-chemical features suggest that the MNP-loaded PLGA nanoparticles obtained are good candidates for intravenous or intratumoral administration.

The equipment of Dynamic Light Scattering (Dynamic Light Scattering) of NANBIOSIS Unit 12 has been used to determine the size distribution of polymer particles and Microscopy with Hyperspectral Analysis (Hyperspectral enhanced dark field microscopy) to detect the encapsulation of magnetic nanoparticles in polymer particles.

Article of reference:

https://doi.org/10.1016/j.colsurfb.2017.09.060

Graphical abstract: Schematic representation of the preparation process of Fe3O4 MHighlightsN P-loaded PLGA nanoparticles by nano-emulsion templating.

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Intracellular trafficking of a dynein-based nanoparticle designed for gene delivery

Unit 1 of NANBIOSIS, Protein Production Platform (PPP) and the  Nanobiotechnology research group of CIBER-BBN in collaboration with the Universidade Estadual de Campinas and the Universidade de São Paulo have recently published, in the European Journal of Pharmaceutical Sciences, the results of the research devoted to the improvement of protein-only based nanoconjugates for gene therapy. The evaluated gene-therapy vehicle prototype  displayed a similar transfection efficiency to that of the commercial vector LipofectamineTM 2000.

Article of reference:

https://doi.org/10.1016/j.ejps.2017.11.002

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Unit 13 of NANBIOSIS participates in a new European project that will boost the Organ-on-Chip technology

The research group coordinating NANBIOSIS Unit 13 is the Spanish group of the European project ORCHID (Organ-On-Chip In Development). The scientists  of Engineering Research Institute (I3A) and CIBER-BBN, Luis Fernández and Iñaki Ochoa, will work on this project whose objective is to accelerate the social and economic impact of the technology known as Organ-on-Chip. This technology based on the use of microfluidic platforms is already facilitating the discovery of drugs, but it can go a step further with applications in personalized medicine and safety pharmacology and that, in addition, offers alternatives to conventional tests in animals. The mechanical properties and research ability of the microfluidic platforms will be tested in NANBIOSIS  unit U13 Tissue and Scaffold Characterization.

 

The project that will take place over two years, is led by the Medical Center of the University of Leiden and the Dutch consortium Organ-on-Chip hDMT and participated by entities and research centers from four other countries, Germany, Belgium, France and the Netherlands. The consortium that has the financial support of the European Union with half a million euros, will work to facilitate and accelerate the development of prototypes, validated cellular systems that mimic sick or healthy human tissue and the implementation of this technology by a broad group of potential users in science, health care and industry. This platform will provide an overview and updates so that users can easily track progress, consult developers directly and identify gaps in current knowledge, which limits implementation. It will also address ethical and regulatory issues, particularly with regard to personalized information, the economic and social impact, the training of researchers and the design of a R & D “roadmap”.

 

Likewise, the construction of an infrastructure is planned so that scientists, policy makers, financiers and end users can join the decision-making processes that will guide future European developments in Organ-on-Chip applications. Among its actions is the establishment of a digital platform that allows the exchange of knowledge between researchers and representatives of private corporations, including insurance companies, pharmaceutical and biotechnology companies, the food industry, health foundations and patient organizations.

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Posters presentation by NANBIOSIS Units in CIBER-BBN ANNUAL CONFERENCE 2017

Last 13 and 14 of November, CIBER-BBN  has celebrated its 11th Annual Conference in Hotel Santemar in Santander. In this conference there was a poster session with the participation of the following Units of NANBIOSIS. Special mention deserves Unit 1 with Neus Ferrer as Director and  Paolo Saccardo as Coordinator (in the picture):

Posters:

U1. Protein Production Platform (PPP):

Engineering protein complexes as nano- or micro-structured vehicles or drugs for human and veterinary medicine. Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, José Vicente Carratalá, Olivia Cano-Garrido, Mercedes Márquez, Paolo Saccardo, Rosa Mendoza, Raquel Díaz, Héctor, López-Laguna, Julieta Sánchez, Anna Obando, Amanda Muñoz, Andrés Cisneros, Eric Voltà, Aida Carreño, José Luis Corchero, Neus Ferrer-Miralles, Esther Vázquez, Antonio Villaverde.

Units  U1. Protein Production Platform (PPP) and U18. Nanotoxicology Unit:

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles. Mireia Pesarrodona, Eva Crosa, Rafael Cubarsi, Alejandro Sanchez-Chardi, Paolo Saccardo, Ugutz Unzueta, Fabian Rueda, Laura Sanchez-Garcia, Naroa Serna, Ramón Mangues, Neus Ferrer Miralles, Esther Vázquez, Antonio Villaverde.

Units U3. Synthesis of Peptides UnitU6. Biomaterial Processing and Nanostructuring Unit, and U20. In Vivo Experimental Platform:

Synthesis of different length monodisperse COL-PEG-PEPTIDE to increase biodisponibility of multifunctional nanovesicles for Fabry’s desease. Edgar Cristóbal-Lecina; Daniel Pulido; Solène Passemard; Elizabet González-Mira; Jaume Veciana; Nora Ventosa; Simó Schwartz; Ibane Abasolo; Fernando Albericio and Miriam Royo.

Units U13. Tissue & Scaffold Characterization Unit and U17. Confocal Microscopy Service::

Preclinical behavior of medium-chain cyanoacrylate glue with two different surgical application forms for mesh fixation in abdominal wall repair. Gemma Pascual, Bárbara Pérez-Köhler, Marta Rodríguez, Claudia Mesa-Ciller, Ángel Ortillés, Estefanía Peña, Begoña Calvo, Juan M. Bellón.

Units U27. High Performance Computing and U8. Micro – Nano Technology Unit:

Inspiration and Expiration Dynamics in Acute Emotional Stress Assessment. Javier Milagro, Eduardo Gil, Jorge M. Garzón-Rey, Jordi Aguiló, Raquel Bailón.

U5. Rapid Prototyping Unit:

Poly-DL-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells. Ana de la Mata, Miguel Ángel Mateos-Timoneda, Teresa Nieto-Miguel, Sara Galindo, Marina López-Paniagua, Xavier Puñet, Elisabeth Engel, Margarita Calonge.

U6. Biomaterial Processing and Nanostructuring Unit:

Strategy for engineering myoglobin nano-traps for biomedical sensing technology. E. Laukhina, O. V. Sinitsyna, N. K. Davydova, V. N. Sergeev, A. Gomez, I. Ratera, C. Blázquez Bondia, J. Paradowska, X. Rodriguez, J. Guasch, Jaume Veciana.

Structure and nanomechanics of quatsome membranes. B. Gumí-Audenis, L. PasquinaLemonche, J.A. Durán, N. Grimaldi, F. Sanz, J. Veciana, I. Ratera, N. Ventosa and M.I. Giannotti

U7. Nanotechnology Unit:

Bioreceptors nanostructuration study for early detection of Alzheimer. José Marrugo, Dr. Samuel Dulay, Dr. Mònica Mir, Prof. Josep Samitier.

RGD dendrimer-based nanopatterns promote chondrogenesis and intercellular communication for cartilage regeneration. Ignasi Casanellas, Anna Lagunas, Iro Tsintzou, Yolanda Vida, Daniel Collado, Ezequiel Pérez-Inestrosa, Cristina Rodríguez, Joana Magalhães, José A. Andrades, José Becerra, Josep Samitier.

Long-range electron transfer between redox partner proteins. Anna Lagunas, Alejandra GuerraCastellano, Alba Nin-Hill, Irene Díaz-Moreno, Miguel A. De la Rosa, Josep Samitier, Carme Rovira, Pau Gorostiza.

U8. Micro – Nano Technology Unit:

Miniaturized multi-sensing platform for pH and Dissolved Oxygen monitoring in Organ-On-aChip systems. M. Zea, A. Moya, I. Gimenez, R. Villa, G. Gabriel.

Electrochemical characterization of SWCNTs based microelectrodes fabricated by inkjet printing. M. Mass, A. Moya, G. Longinotti, M. Zea, M. Muñoz, E. Ramon, L. Fraigi, R. Villa, G. Ybarra, G. Gabriel.

U9. Synthesis of Nanoparticles Unit:

In vivo imaging and local persistance of polymeric micro- and nanomaterials labelled with the near infrared dye IR820. Isabel Ortiz de Solórzano, Gracia Mendoza, Inmaculada Pintre, Sara García-Salinas, Víctor Sebastián, Vanesa Andreu, Marina Gimeno, Manuel Arruebo.

U10. Drug Formulation:

Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids. Santiago Grijalvo, Adele Alagia, Gustavo Puras, Jon Zárate, Judith Mayr, José Luis Pedraz, Ramon Eritja

U12. Nanostructured liquid characterization unit:

Perfluorocarbon-loaded Nanocapsules from Nano-emulsion Templates as Microbubble Precursors for Biomedical Applications. G. Calderó, A. González, M. Monge, C. Rodríguez-Abreu, M.J.García-Celma, C. Solans.

Biodistribution study of polymeric drug-loaded nanoparticles in murine model. Marta Monge, Aurora Dols, Stephane Fourcade, Aurora Pujol, Carlos Rodríguez-Abreu, Conxita Solans.

U16. Surface Characterization and Calorimetry Unit:

Behavior and a comparative study between tantalum and titanium alloy implant surfaces against bacterial adhesion. M.A. Pacha-Olivenza, M.L. González-Martín.

Bacterial adhesion on calcium ion-modified titanium implant surfaces. M.A. Pacha Olivenza, R. Tejero, M. Delgado-Rastrollo, M.L. González-Martín.

Bioactive coatings to promote tissue regeneration and ingrowth into 3D custom-made porous titanium endoimplants (COATREG-3D). Santos-Ruiz L; Granados JF; Ruiz F; Yáñez JI; González A; Cabeza N; Vida Y; Pérez-Inestrosa E; Izquierdo-Barba I; Vallet-Regí M; Rubio J; Orgaz F; Rubio N; González ML; Peris JL; Monopoli D; Becerra J.

U17. Confocal Microscopy Service:

Subcutaneous implantation of a biodegradable apatite/agarose scaffold: biocompatibility and osteogenesis characterization in a rat model. Natalio García-Honduvilla, Gemma Pascual, Miguel A. Ortega, Alejandro Coca, Cynthia Trejo, Jesús Román, Juan Peña, María V. Cabañas, Julia Buján, and María Vallet-Regí.

U25. NMR: Biomedical Applications I:

Dual T1/T2 NCP-based novel contrast agents for brain tumor MRI: a preclinical study. Suarez, S; Arias-Ramos, N; Candiota, AP; Lorenzo, J; Ruiz-Molina, D; Arús, C; Novio, F.

Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide. Ferrer-Font, L; Arias-Ramos, N; Lope-Piedrafita, S; Julià- Sapé, M; Pumarola, M; Arús, C; Candiota, AP.

U26. NMR: Biomedical Applications II:

Gated nanodevices for innovative medical therapies. Maria Alfonso, Irene Galiana, Beatriz Lozano, Borja Diaz de Greñu, Cristina de la Torre, Andrea Bernardos, Sameh El Sayed, Daniel MuñozEspin, Miguel Rovira, José Ramón Murguía, Manuel Serrano, Ramón Martínez-Máñez.

NANOPROBE: Gated sensing materials and devices for the detection of infectious diseases and urological cancer. Ángela Ribes, Luís Pla, Sara Santiago-Felipe, Alba Loras-Monfort, M.Carmen Martínez-Bisbal, Elena Aznar, Guillermo Quintás-Soriano, José Luis Ruiz-Cerdá, María Angeles.

 

 

 

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NANBIOSIS in CIBER-BBN ANNUAL CONFERENCE 2017

CIBER-BBN will celebrate its 11th Annual Conference on November 13 and 14 in Santander. In these conference there will be a session dedicated to NANBIOSIS. Likewise, the annual meeting of the Scientific Technical Advisory Committee of NANBIOSIS will take place.

As in previous occasions, the meeting will serve to know the activity of NANBIOSIS, the Singular Technical Scientific Infrastructure (ICTS) of the CIBER-BBN and the Minimally Invasive Surgery Center Jesus Usón for the production and characterization of biomaterials, nanomaterials and devices up to its preclinical validation.

As a novelty, it will be presented at the conference, the new internal structure, generated by NANBIOSIS for the development of “turnkey” projects in which, taking advantage of the complementarity and experience of its Units, NANBIOSIS offers complete service packages, with added value, adapted to the client’s needs, for applications such as nanotherapeutic agents, regenerative medicine, medical and diagnostic devices, among others. Some of the packages that are already designed or in more advanced stages will be explained, among which stands out the service of characterization and cascade assessment of nanomaterials that includes the characterization of the physicochemical attributes, their biological properties in vitro (immunology, toxicology and efficacy), and its in vivo compatibility (immunology, toxicology and efficacy), using appropriate animal models, with the possibility of being subject to regulatory conditions of Good Laboratory Practices. Some success stories of these “turnkey” projects developed in NANBIOSIS will be shown.

On this occasion, in addition, it is planned a presentation of EATRIS , the European Infrastructure for the Translation of Medicine, with which NANBIOSIS has initiated a line of collaboration.

Since its launch in July 2015, NANBIOSIS has received more than 550 access requests through its website, with an average participation of some 80 competitive projects per year and with an annual income for its services of between 2 and 3 million euros. Among its users, there are more than 100 companies.

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NANBIOSIS presented at the 12th annual event of the ETPN

During the days 17-19 of October Malaga has hosted the 12th annual event of European Platform of Technology in Nanomedicine (ETPN), a European meeting of 200 experts in research and innovation in nanomedicine.

The meeting was organized by Bionand, the Spanish Platform of Nanomedicine (Nanomed Spain), the Institute of Nanoscience of Madrid (Imdea) and the Center for Biomedical Research Network in the area of ​​Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), partner of NANBIOSIS.

During the event, the ETPN General Assembly took place as well as parallel meetings of the specialized working groups on different scientific and cross-cutting aspects related to nanomedicine

In this framework, the ICTS NANBIOSIS has been presented by the Scientific Director of CIBER-BBN, Ramón Martínez Máñez, to the European Nanomedicine community.

EUROPEAN TECHNICAL PLATFORM OF NANOMEDICINE

The European Technology Platforms are a key element in the European field of innovation, associations born with the mission of sharing knowledge, mobilizing the actors involved and developing sector strategies, all based on the social challenges established by the European Commission and with the ultimate goal of its translation to the market.

The European Nanomedicine Technology Platform (ETPN) was created in 2005 by the European Commission and a group of experts from academia and industry who have since contributed to the publication of various strategic documents identifying the needs and the roadmaps for research in Nanomedicine in Europe. Its main objectives are to establish a clear strategic vision of the sector, to reduce the fragmentation of nanomedical research, to mobilize public and private investment, to identify priority areas, to promote innovation in nanobiotechnologies for medical use and to strengthen Europe’s competitiveness in this sector scientific and industrial level

Currently, the ETPN has more than 120 members from 25 countries, representing all actors involved in nanomedicine, such as academic institutions, research centers, small and medium enterprises, industry, public agencies, representatives of the platforms the European Commission itself, among others.

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Nanomedicine Summer School

The second Summer School in Nanomedicine coordinated by Simó Schwartz, Scientific Director of NANBIOSIS unit 20,  was held at Vall d’Hebron hospital on 28 and 29 September. Dr. Schwartz has been the president of the European Society for Nanomedicine (ESNAM), a European scientific society focused on the clinical application of nanomedicine. From this society tasks are carried out to promote the research and the use of nanomedicine in the health sector, as well as to facilitate the exchange of knowledge in this area at European level among all the actors involved, Academy, industry and entities regulators.

CIBER-BBN, partner of NANBIOSIS, as sponsor of ESNAM, has collaborated in the organization of this event. Lectures were given by some Scientific Directors  or Coordinators  of NANBIOSIS units as Jaume Veciana, Ibane Abasolo, Laura Lechuga and Antoni Villaverde .

Photos of the meeting can be viewed in this link.

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JUMISC, partner of NANBIOSIS, represents Spain in a European network of 22 countries

The Jesús Usón Minimally Invasive Surgery Centre (JUMISC), partner of NANBIOSIS toguether with CIBER-BBN,  leads a multidisciplinary European research network to improve present urinary stents and prevent their causes of failure.

The idea of creating the network was born from a research, started in 1999 by Doctor Soria, Researcher-Coordinator of the Endoscopic Surgery Area at the JUMISC and the promoter of the mentioned network, representing Spain.

His proposal has been supported by the European and Spanish Urology Association, and funded by the Horizon 2020 Program-Cost Actions (European Cooperation in Science and Technology)

The focus of this Action is to create a multidisciplinary team to identify the problems concerning the urinary stents (design, composition, biomaterial applications, coatings, incrustation, etc.) and to promote future research on this field. In this way, the network will try to reduce adverse effects provoked by the present stents.

This European network (2017-2021), coordinated by Dr. Soria, the Chair of the Action, is composed by 22 European countries and other proposals coming from USA,  Japan, South Korea,  Israel, Canada, Russia, India and it is open to other invited countries to cooperate inside  the organised working groups.

This action will provide, during the next 4 years, an extensive and interdisciplinary R&D program to discover the causes of failure of the present stents and will propose cooperative work in urology and bioengineering field.

This proposal, an initiative of the JUMISC, leaded by Doctor Sánchez Margallo, will contribute to improve healthy-quality of patients, reduce in health care costs, and increase the competitiveness of the European medical device industry.

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New Zealand White rabbit as a model for preclinical studies addressing tissue repair at the level of the abdominal wall.

Juan Manuel Bellón and Gemma Pascual, Scientific Director and Coordinator of Unit 17 of NANBIOSIS, have recently published an article in the prestigious journal Tissue Eng Part C Methods.

Once a prosthetic material is implanted, an inflammatory reaction is induced in an attempt to remove it or isolate it from the host tissue. After this initial response, a cellular response takes place that gives rise to the start of the process of integration of the biomaterial within the host tissue. Immunohistochemical studies can provide information on the events that regulate this process, and are useful to analyze the progression of the implant and the neoformed tissue. For the tissue repair of a damaged area constantly subjected to tensile forces such as the abdominal wall, optimal collagenization is an extremely important factor. The proper deposition and organization of mainly collagen type I in the neoformed scar tissue will condition the mechanical strength and compliance of the repair zone and thus possible hernia recurrence. In this report, we review the use of the New Zealand White rabbit as the experimental animal for several models of abdominal wall repair and among other techniques, collagen component of the implants was assessed by immunofluorescence using anti-collagen type I and type III monoclonal antibodies. Samples were examined using a confocal microscope Leica SP5 belonging to the platform ICTS ‘NANBIOSIS’ U17 of the CIBER-BBN at the University of Alcalá.

Important information gained from selected models was observed in terms of tissue ingrowth and collagen deposition in the implant area showing significant differences depending on the properties of the implanted prosthetic material. Some variations were also observed in biomechanical properties according to the components comprising each prosthetic material.

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Best Abstract award at the European Society for Surgical Research meeting

Verónica Gómez-Gil, collaborator in Unit 17 of NANBIOSIS and the GITBIT-UAH group (CIBER-BBN), has been the first prizewinner in the Best Abstract Competition  at the symposium “New horizons in prevention and treatment of adhesions” organized by the Dutch Adhesion Group (DAG) at the 52nd meeting of the European Society for Surgical Reseach (ESSR). The ESSR 2017 meeting was held in Amsterdam from 14th till 17th June. The title of the abstract, presented as a quick-shot presentation and a full oral during the congress, was: An experimental adhesiogenic model to evaluate histological events over time in the omentum during adhesion formation.

This work shows that distribution of soluble and membrane-bound form of betaglycan, together with the expression of TGF-β1 and TGF-β3 at each time point after adhesion formation, are key factors to the cytoarchitecture and composition of omental adhesion tissue. These findings are of interest in the design of new adhesion prevention strategies.

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