Grupos Investigadores

Miembros del Grupo

Coordinador
Peñuelas Sánchez, Iván
(ipenuelas@unav.es)
Investigadores
María
Collantes Martínez
Gemma
Quincoces Fernández
Jon Ander
Simon Martínez
Colaboradores
María
De Arcocha Torres
Marga
Ecay Ilzarbe
Álvaro
Erhard García
Rocio
Ramos Membrive
Marta
Rúa Gómez

Líneas de Investigación

  • Biodistrubución in vivo mediante imagen molecular de compuestos radiomarcados
  • Imagen metabólica y funcional in vivo mediante PET/SPECT-CT en modelos animales
  • Nanosistemas radiomarcados
  • Radiofarmacia y radioquímica PET/SPECT
  • Radionanofarmacología

Palabras Clave

  • Biodistribución in vivo
  • Imagen molecular PET/SPECT
  • MicroPET
  • Nanopartículas radiomarcadas
  • Radiofarmacia PET/SPECT

Publicaciones Científicas desde 2018

  • Autores: Kiss, O. C. (Autor de correspondencia); Scott, P. J. H.; Peñuelas Sánchez, Iván; et al.
    Revista: EJNMMI RADIOPHARMACY AND CHEMISTRY
    ISSN: 2365-421X Vol.8 N° 1 2023 págs. 6
    Resumen
    Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main body: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field, and include new PET-labelling methods for 11C and 18F, the importance of choosing the proper chelator for a given radioactive metal ion, implications of total body PET on use of radiopharmaceuticals, legislation issues and radionuclide therapy including the emerging role of 161Tb.
  • Autores: Utomo, E.; Domínguez-Robles, J.; Moreno-Castellanos, N.; et al.
    Revista: INTERNATIONAL JOURNAL OF PHARMACEUTICS
    ISSN: 0378-5173 Vol.630 2023 págs. 122475
  • Autores: Simón Martínez, Jon Ander; Utomo, E.; Pareja Del Rio, Felix; et al.
    Revista: PHARMACEUTICS
    ISSN: 1999-4923 Vol.15 N° 3 2023 págs. 843
    Resumen
    The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I- took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.
  • Autores: Rúa Gómez, Marta; Simón Martínez, Jon Ander; Collantes Martínez, María (Autor de correspondencia); et al.
    Revista: FRONTIERS IN MICROBIOLOGY
    ISSN: 1664-302X Vol.14 2023 págs. 1094929
    Resumen
    IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[F-18] fluoro-D-glucose: [F-18]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms. MethodsWe tested two specific radiotracers: 2-deoxy-2-[F-18]-fluoro-D-sorbitol ([F-18]FDS) and 2-[F-18]F-rho-aminobenzoic acid ([F-18]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection. Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [F-18]FDG in vitro. [F-18]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [F-18]FPABA. Furthermore, [F-18]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species.
  • Autores: Peñalva Sobrón, Rebeca; Martínez López, Ana Luisa; Gamazo de la Rasilla, Carlos Manuel; et al.
    Revista: FOOD HYDROCOLLOIDS
    ISSN: 0268-005X Vol.136 N° Part. A 2023 págs. 108213
    Resumen
    The current work describes the capability of casein-chitosan microparticles to encapsulate Lactobacillus plantarum (CECT 220 and WCFS1 strains) and evaluates their ability to target the distal areas of the gut and to stimulate the immune system. Microparticles were prepared by complex coacervation, between sodium caseinate and chitosan in an aqueous suspension of the bacteria, and dried by spray-drying. In order to increase the survival rate of the loaded bacteria, microparticles were cross-linked with one of the following cross-linkers: tripolyphosphate, calcium salts or vanillin.Overall, microparticles displayed a mean size of about 7.5 mu m with a bacteria loading of about 11 Log CFU/g, when cross-linked with vanillin (MP-LP-V). For conventional microparticles, the payload was 10.12 Log CFU/g. The storage stability study at 25 degrees C/60% RH, MP-LP-V offered the highest degree of protection without signif-icant modification of the payload in 260 days. Compared with control (aqueous suspension of bacteria), MP-LP-V also displayed a significantly higher degree of protection against probiotic inactivation in simulated gastric and intestinal fluids. In vivo results evidenced that microparticles, orally administered to rats, were able to reach the distal ileum and colon in about 4 h post-administration. Additionally, the effect of the daily administration of 107 CFU/mouse of MP-LP-V, for 3 weeks, induced an immunomodulatory effect characterized by an important enhancement of Th1 and Th17 responses. In conclusion, these microparticles seem to be a promising strategy for increasing survival and efficacy of probiotics, allowing the formulation of cost-effective and more stable and effective probiotic-based nutraceuticals.
  • Autores: Guedj, E. (Autor de correspondencia); Varrone, A.; Boellaard, R.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° 6 2022 págs. 2100 - 2101
  • Autores: Guedj, E. (Autor de correspondencia); Varrone, A.; Boellaard, R.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° 2 2022 págs. 632 - 651
    Resumen
    The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [F-18]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [F-18]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [F-18]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.
  • Autores: Collantes Martínez, María (Autor de correspondencia); Vairo, C.; Erhard García, Álvaro; et al.
    Revista: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
    ISSN: 0939-6411 Vol.177 2022 págs. 61 - 67
    Resumen
    Negatively charged microspheres (NCMs) are postulated as a new form of treatment for chronic wounds. Despite the efficacy shown at clinical level, more studies are required to demonstrate their safety and local effect. The objective of the work was to confirm the lack of NCM systemic absorption performing a biodistribution study of the NCMs in an open wound rat animal model. To this end, radiolabeling of NCMs with technetium-99m was optimized and biodistribution studies were performed by in vivo SPEC/CT imaging and ex vivo counting during 24 h after topical administration. The studies were performed on animals treated with a single or repeated dose to study the effect of macrophages during a prolonged treatment. NCM radiolabeling was achieved in a simple, efficient and stable manner with high yield. SPECT/CT images showed that almost all NCMs (about 85 %) remained on the wound for 24 h either after single or multiple administrations. Ex vivo biodistribution studies confirmed that there was no accumulation of NCMs in any organ or tissue except in the wound area, suggesting a lack of absorption. In conclusion, NCMs can be considered safe as local wound treatment since they remain at the administration area.
  • Autores: Utomo, E.; Domínguez-Robles, J.; Moreno-Castellanos, N.; et al.
    Revista: INTERNATIONAL JOURNAL OF PHARMACEUTICS
    ISSN: 0378-5173 Vol.624 2022 págs. 122061
    Resumen
    In this work the preparation and characterisation of intranasal implants for the delivery of risperidone (RIS) is described. The aim of this work is to develop better therapies to treat chronic conditions affecting the brain such as schizophrenia. This type of systems combines the advantages of intranasal drug delivery with sustained drug release. The resulting implants were prepared using biodegradable materials, including poly(caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA). These polymers were combined with water-soluble compounds, such as poly(ethylene glycol) (PEG) 600, PEG 3000, and Tween (R) 80 using a solvent-casting method. The resulting implants contained RIS loadings ranging between 25 and 50 %. The obtained implants were characterised using a range of techniques including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM). Moreover, in vitro RIS release was evaluated showing that the addition of watersoluble compounds exhibited significant faster release profiles compared to pristine PCL and PLGA-based implants. Interestingly, PCL-based implants containing 25 % of RIS and PLGA-based implants loaded with 50 % of RIS showed sustained drug release profiles up to 90 days. The former showed faster release rates over the first 28 days but after this period PLGA implants presented higher release rates. The permeability of RIS released from the implants through a model membrane simulating nasal mucosa was subsequently evaluated showing desirable permeation rate of around 2 mg/day. Finally, following in vitro biocompatibility studies, PCL and PLGA-based implants showed acceptable biocompatibility. These results suggested that the resulting implants displayed potential of providing prolonged drug release for brain-targeting drugs.
  • Autores: Molinet Dronda, Francisco; Blesa de los Mozos, Francisco Javier; López-González del Rey, N.; et al.
    Revista: NEUROBIOLOGY OF DISEASE
    ISSN: 0969-9961 Vol.167 2022 págs. 105669
    Resumen
    Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.
  • Autores: Collantes Martínez, María; Simon, J.; Shahrour, Hawraa; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° SUPPL 1 2022 págs. S445 - S445
  • Autores: Simón Martínez, Jon Ander; Collantes Martínez, María; Pareja Del Rio, Felix; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° Supl. 1 2022 págs. S663
  • Autores: Pareja Del Rio, Felix; Salinas, V.; Passannante, R.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° Supl. 1 2022 págs. S449
  • Autores: Peñuelas Sánchez, Iván; Simón Martínez, Jon Ander; Otero, A.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° Supl. 1 2022 págs. S446 - S447
  • Autores: Collantes Martínez, María; Rúa Gómez, Marta; Simón, J. A.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° Supl. 1 2022 págs. S446
  • Autores: Simón, J.; Pulagam, K. R.; Rúa Gómez, Marta; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° Supl. 1 2022 págs. S239
  • Autores: Collantes Martínez, María; Rúa Gómez, Marta; Simón, J. A.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.49 N° Supl. 1 2022 págs. S448 - S449
  • Autores: Ramos Membrive, Rocio; Erhard García, Álvaro; Luis de Redín Subirá, Inés; et al.
    Revista: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
    ISSN: 1773-2247 Vol.64 2021 págs. 101809
    Resumen
    The aim of this work was to study the biodistribution of bevacizumab-loaded HSA nanoparticles (NP-Ab) crosslinked with PEG35000 by SPECT/CT in vivo imaging. For this purpose, NP-Abs were prepared by a desolvation process, coated with PEG35000 and radiolabeled with technetium-99 m using a pre-tinning method ([99mTc]TcNP-Ab). The Ab was labeled using [99mTc][Tc(CO)3(H2O)3]+ and used to prepare nanoparticles (NP-[99mTc]TcAb). Particle size was similar in both formulations. Chemical and radiochemical purity of the two nanosystems were >95%. Bevacizumab-labeling conditions were tested by in vitro stability studies. More than 87% of the radiolabeled antibody remained intact for 24 h after incubation with plasma. SPECT/CT imaging of the two nanoparticles was performed in healthy female Wistar rats. Ex vivo gamma counting of selected organs was also carried out in all animals. The results showed different clearance rates of the nanoparticle shell and the antibody, providing valuable information by the use of molecular imaging in the evaluation of drug delivery nanosystems.
  • Autores: Garrido, V.; Piñero-Lambea, C.; Rodríguez-Arce, I.; et al.
    Revista: MOLECULAR SYSTEMS BIOLOGY
    ISSN: 1744-4292 Vol.17 N° 10 2021 págs. e10145
    Resumen
    Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.
  • Autores: Collantes Martínez, María; Ecay Ilzarbe, Marga; Quincoces Fernández, Gemma; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.48 N° SUPPL 1 2021 págs. S252 - S253
  • Autores: Morbelli, S. (Autor de correspondencia); Ekmekcioglu, O.; Barthel, H. ; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.47 N° 11 2020 págs. 2487 - 2492
  • Autores: Morbelli, S.; Esposito, G.; Arbizu Lostao, Javier; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.47 N° 8 2020 págs. 1885 - 1912
    Resumen
    Purpose This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. Methods Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [F-18]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [F-18]fluorodopa imaging in this setting are still lacking. Conclusion All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.
  • Autores: Irurzun Arana, Itziar (Autor de correspondencia); Asín Prieto, Eduardo; Martín Algarra, Salvador; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.10 N° 1 2020 págs. 7478
    Resumen
    Advanced melanoma remains a disease with poor prognosis. Several serologic markers have been investigated to help monitoring and prognostication, but to date only lactate dehydrogenase (LDH) has been validated as a standard prognostic factor biomarker for this disease by the American Joint Committee on Cancer. In this work, we built a semi-mechanistic model to explore the relationship between the time course of several circulating biomarkers and overall or progression free survival in advanced melanoma patients treated with adjuvant high-dose interferon-alpha 2b. Additionally, due to the adverse interferon tolerability, a semi-mechanistic model describing the side effects of the treatment in the absolute neutrophil counts is proposed in order to simultaneously analyze the benefits and toxic effects of this treatment. The results of our analysis suggest that the relative change from baseline of LDH was the most significant predictor of the overall survival of the patients. Unfortunately, there was no significant difference in the proportion of patients with elevated serum biomarkers between the patients who recurred and those who remained free of disease. Still, we believe that the modelling framework presented in this work of circulating biomarkers and adverse effects could constitute an additional strategy for disease monitoring in advance melanoma patients.
  • Autores: de Arcocha-Torres, M. (Autor de correspondencia); Quincoces Fernández, Gemma; Martinez-Lopez, A. L.; et al.
    Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
    ISSN: 2253-654X Vol.39 N° 4 2020 págs. 225 - 232
  • Autores: Torres, M. D. ; Quincoces Fernández, Gemma; Martínez López, Ana Luisa; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.47 N° SUPPL 1 2020 págs. S673 - S674
  • Autores: Vairo, C.; Collantes Martínez, María; Quincoces Fernández, Gemma; et al.
    Revista: INTERNATIONAL JOURNAL OF PHARMACEUTICS
    ISSN: 0378-5173 Vol.569 2019 págs. 118484
    Resumen
    Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers (NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99 m (99mTc-NLC) as radiomarker, topically administered on a wound. 99mTc-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.
  • Autores: Inchaurraga Casadamón, Laura; Martínez-López, A. L. ; Abdulkarim, M. ; et al.
    Revista: INTERNATIONAL JOURNAL OF PHARMACEUTICS. X
    ISSN: 2590-1567 Vol.1 2019 págs. 100006
    Resumen
    The aim of this work was to evaluate the mucus-permeating properties of nanocarriers using zein nanoparticles (NPZ) coated with a Gantrez (R) AN-thiamine conjugate (GT). NPZ were coated by incubation at different GT-to-zein ratios: 2.5% coating with GT (GT-NPZ1), 5% (GT-NPZ2) and 10% (GT-NPZ3). During the process, the GT conjugate formed a polymer layer around the surface of zein nanoparticles. For GT-NPZ2, the thickness of this corona was estimated between 15 and 20 nm. These nanocarriers displayed a more negative zeta potential than uncoated NPZ. The diffusivity of nanoparticles was evaluated in pig intestinal mucus by multiple particle tracking analysis. GT-NPZ2 displayed a 28-fold higher diffusion coefficient within the mucus layer than NPZ particles. These results align with in vivo biodistribution studies in which NPZ displayed a localisation restricted to the mucus layer, whereas GT-NPZ2 were capable of reaching the intestinal epithelium. The gastro-intestinal transit of mucoadhesive (NPZ) and mucus-permeating nanoparticles (GT-NPZ2) was also found to be different. Thus, mucoadhesive nanoparticles displayed a significant accumulation in the stomach of animals, whereas mucus-penetrating nanoparticles appeared to exit the stomach more rapidly to access the small intestine of animals.
  • Autores: Brotons Cantó, Ana; Gamazo de la Rasilla, Carlos Manuel; Martín Arbella, Nekane; et al.
    Revista: JOURNAL OF PHARMACEUTICAL SCIENCES
    ISSN: 0022-3549 Vol.108 N° 7 2019 págs. 2421 - 2429
    Resumen
    Peanut allergy is one of the most prevalent and severe of food allergies with no available cure. The aim of this work was to evaluate the potential of an oral immunotherapy based on the use of a roasted peanut extract encapsulated in nanoparticles with immunoadjuvant properties. For this, a polymer conjugate formed by the covalent binding of mannosamine to the copolymer of methyl vinyl ether and maleic anhydride was first synthetized and characterized. Then, the conjugate was used to prepare nanoparticles with an important capability to diffuse through the mucus layer and reach, in a large extent, the intestinal epithelium, including Peyer's patches. Their immunotherapeutic potential was evaluated in a model of presensitized CD1 mice to peanut. After completing therapy, mice underwent an intraperitoneal challenge with peanut extract. Nanoparticle-treatment was associated with both less serious anaphylaxis symptoms and higher survival rates than control, confirming the protective effect of this formulation against the challenge.
  • Autores: Inchaurraga Casadamón, Laura; Martinez-Lopez, A. L.; Cattoz, B.; et al.
    Revista: EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
    ISSN: 0928-0987 Vol.128 2019 págs. 81 - 90
    Resumen
    Thiamine-coated nanoparticles were prepared by two different preparative methods and evaluated to compare their mucus-penetrating properties and fate in vivo. The first method of preparation consisted of surface modification of freshly poly(anhydride) nanoparticles (NP) by simple incubation with thiamine (T-NPA). The second procedure focused on the preparation and characterization of a new polymeric conjugate between the poly (anhydride) backbone and thiamine prior the nanoparticle formation (T-NPB). The resulting nanoparticles displayed comparable sizes (about 200 nm) and slightly negative surface charges. For T-NPA, the amount of thiamine associated to the surface of the nanoparticles was 15 mu g/mg. For in vivo studies, nanoparticles were labelled with either Tc-99m or Lumogen (R) Red. T-NPA and T-NPB moved faster from the stomach to the small intestine than naked nanoparticles. Two hours post-administration, for T-NPA and T-NPB, > 30% of the given dose was found in close contact with the intestinal mucosa, compared with a 13.5% for NP. Interestingly, both types of thiamine-coated nanoparticles showed a greater ability to cross the mucus layer and interact with the surface of the intestinal epithelium than NP, which remained adhered in the mucus layer. Four hours post-administration, around 35% of T-NPA and T-NPB were localized in the ileum of animals. Overall, both preparative processes yielded thiamine decorated carriers with similar physico-chemical and biodistribution properties, increasing the versatility of these nanocarriers as oral delivery systems for a number of biologically active compounds.
  • Autores: Rúa Gómez, Marta; Simón, Jan; Collantes Martínez, María; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.46 N° SUPPL 1 2019 págs. S316 - S316
  • Autores: Simón, Jan; Erhard García, Álvaro; Quincoces Fernández, Gemma; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.46 N° SUPPL 1 2019 págs. S316 - S316
  • Autores: González Aseguinolaza, Gloria; Collantes Martínez, María; Ecay Ilzarbe, Marga; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN: 0168-8278 Vol.70 N° 1 2019 págs. E583
  • Autores: Gonzalez-Aseguinolaza, G.; Collantes Martínez, María; Moreno-Luqui, D.; et al.
    Revista: HUMAN GENE THERAPY
    ISSN: 1043-0342 Vol.30 N° 11 2019 págs. A152 - A153
  • Autores: Quincoces Fernández, Gemma; Erhard García, Álvaro; Collantes Martínez, María; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.46 N° SUPPL 1 2019 págs. S315 - S316
  • Autores: Benichou, B.; Collantes Martínez, María; Moreno Luqui, Daniel; et al.
    Revista: MOLECULAR THERAPY
    ISSN: 1525-0016 Vol.27 N° 4 2019 págs. 197 - 198
  • Autores: Erhard García, Álvaro; Collantes Martínez, María; Gainza., G; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.45 N° Supl. 1 2018 págs. S615
  • Autores: Niu, Z.; Samaridou, E.; Jaumain, E.; et al.
    Revista: JOURNAL OF CONTROLLED RELEASE
    ISSN: 0168-3659 Vol.276 2018 págs. 125-139
  • Autores: Erhard García, Álvaro; Collantes Martínez, María; Gainza, G.; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.45 N° Supl. 1 2018 págs. S615
  • Autores: Collantes Martínez, María; Morales Lozano, María Isabel; Blanco Fernández, Laura; et al.
    Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
    ISSN: 1619-7070 Vol.45 2018 págs. S565 - S566

Proyectos desde 2018

  • Título: Probióticos como agentes inmunomoduladores de vacunas
    Código de expediente: GN2022/04
    Investigador principal: CARLOS MANUEL GAMAZO DE LA RASILLA.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2022 GN Proyectos de Investigación en salud
    Fecha de inicio: 22-12-2022
    Fecha fin: 21-12-2025
    Importe concedido: 79.119,13€
    Otros fondos: -
  • Título: Upgrade para integrar un sistema MicroPET
    Código de expediente: 0011-1508-2022-000035
    Investigador principal: IVAN PEÑUELAS SANCHEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2022 GN adquisición de equipamiento e infraestructuras de I+D
    Fecha de inicio: 12-04-2022
    Fecha fin: 31-12-2022
    Importe concedido: 90.000,00€
    Otros fondos: -
  • Título: Imagen in vivo de la biodistribución de nanovacunas radiomarcadas de administración oral para enfermedades infecciosas (INNAVACORID)
    Código de expediente: PI21/01003
    Investigador principal: IVAN PEÑUELAS SANCHEZ, MARIA COLLANTES MARTINEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2021 AES Proyectos de investigación
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2024
    Importe concedido: 117.370,00€
    Otros fondos: Fondos FEDER
  • Título: UNAV_P07_Msintesis Módulo Automático de Síntesis Radioquímica para la síntesis automatizada de radiotrazadores emisores de positrones
    Código de expediente: 0011-1508-2020-000008 UNAV_P07
    Investigador principal: IVAN PEÑUELAS SANCHEZ, IVAN PEÑUELAS SANCHEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2020 GN adquisición de equipamiento e infraestructuras de I+D
    Fecha de inicio: 27-07-2020
    Fecha fin: 15-11-2020
    Importe concedido: 69.534,94€
    Otros fondos: -
  • Título: Equipo UNAV_P09_SPECT. Sistema integrado MicroSPECT/CT de Imagen Molecular para investigación biomédica preclínica, combinando en un único equipo un sistema MicroSPECT y un CT
    Código de expediente: 0011-1508-2020-000008 UNAV_P09
    Investigador principal: IVAN PEÑUELAS SANCHEZ, IVAN PEÑUELAS SANCHEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2020 GN adquisición de equipamiento e infraestructuras de I+D
    Fecha de inicio: 27-07-2020
    Fecha fin: 15-11-2020
    Importe concedido: 228.100,00€
    Otros fondos: -
  • Título: Nueva terapia fágica frente a infecciones de E. coli en humanos (ANTI-COLI)
    Código de expediente: 0011-1365-2020-000279
    Investigador principal: GUILLERMO MARTINEZ DE TEJADA DE GARAIZABAL, GUILLERMO MARTINEZ DE TEJADA DE GARAIZABAL.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2020 GN I+D Transferencia del conocimiento (empresas)
    Fecha de inicio: 01-04-2020
    Fecha fin: 31-07-2022
    Importe concedido: 224.058,73€
    Otros fondos: Fondos FEDER
  • Título: Vacuna no-parental frente a infecciones por Escherichia coli enteroxigénicas
    Código de expediente: PI19/00416
    Investigador principal: CARLOS MANUEL GAMAZO DE LA RASILLA, JUAN MANUEL IRACHE GARRETA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2022
    Importe concedido: 147.620,00€
    Otros fondos: Fondos FEDER
  • Título: Nuevas combinaciones inmunomoduladoras frente al adenocarcinoma de pulmón según el estado mutacional del oncogen KRAS. Estudio de nuevos biomarcadores de respuesta a terapia anti-PD-1
    Código de expediente: PI19/00678
    Investigador principal: IGNACIO GIL BAZO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2022
    Importe concedido: 111.320,00€
    Otros fondos: Fondos FEDER
  • Título: Desarrollo de nuevos compuestos radiofluorados para el diagnóstico in vivo de infección prótesica articular mediante imagen PET (DIPAPET)
    Código de expediente: PI17/00873
    Investigador principal: IVAN PEÑUELAS SANCHEZ, IVAN PEÑUELAS SANCHEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES2017 PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2021
    Importe concedido: 93.170,00€
    Otros fondos: Fondos FEDER
  • Título: Parkinsonismos asociados a enfermedad de Gaucher: glucocerebrosidasa para el aclaramiento de alfa?sinucleína.
    Código de expediente: 46/2017
    Investigador principal: JOSE LUIS LANCIEGO PEREZ.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2017 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 15-12-2017
    Fecha fin: 14-12-2020
    Importe concedido: 74.106,01€
    Otros fondos: Fondos FEDER
  • Título: NANO-IMMUNOTHERAPY: INTRACELLULAR TARGETING OF CANCER CELLS AND TAMS
    Código de expediente: PCIN-2017-017
    Investigador principal: IVAN PEÑUELAS SANCHEZ, IVAN PEÑUELAS SANCHEZ.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2017 MINECO APCIN
    Fecha de inicio: 01-10-2017
    Fecha fin: 30-06-2021
    Importe concedido: 100.000,00€
    Otros fondos: -
  • Título: Disfunción del tejido adiposo en obesidad, inflamación y envejecimiento: mecanismos implicados y efectos del ejercicio físico y los ácidos grasos omega-3
    Código de expediente: BFU2015-65937-R
    Investigador principal: MARIA JESUS MORENO ALIAGA, SILVIA LORENTE CEBRIAN, MARIA JESUS MORENO ALIAGA, SILVIA LORENTE CEBRIAN.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2015 MINECO RETOS INVESTIGACION. PROYECTOS I+D+i
    Fecha de inicio: 01-01-2016
    Fecha fin: 31-12-2020
    Importe concedido: 169.400,00€
    Otros fondos: Fondos FEDER
  • Título: Desarrollo de una inmunoterapia oral basada en nanopartículas para el tratamiento de alergias alimentarias
    Código de expediente: RTC-2015-3826-1
    Investigador principal: JUAN MANUEL IRACHE GARRETA, JUAN MANUEL IRACHE GARRETA.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2015 MINECORETOS-COLABORACION
    Fecha de inicio: 23-02-2015
    Fecha fin: 30-06-2019
    Importe concedido: 132.700,00€
    Otros fondos: -
  • Título: Efficacy of a gene therapy-based treatment for Wilson
    Investigador principal: IVAN PEÑUELAS SANCHEZ
    Fecha de inicio: 28-03-2018
    Fecha fin: 30-12-2019
    Importe: 0
    Otros fondos: -
  • Título: Biodistribución microesferas Bioadhesivas
    Investigador principal: IVAN PEÑUELAS SANCHEZ
    Fecha de inicio: 11-09-2017
    Fecha fin: 27-11-2018
    Importe: 0
    Otros fondos: -