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U12-S05. Surface and interfacial tensiometry

Surface and interfacial tensiometry

For this service we offer a Sigma 701 force tensiometer (Biolin Scientific) with software for control, acquisition and data treatment for the measurement of surface and interfacial tensions, as well as the automatic determination of critical micellar concentrations. It is equipped with Wilhelmy plate and Du Nouy ring accessories.
We also offer a SITE Spinning Drop Interfacial Tensiometer (Krüss) for determination of liquid-liquid interfacial tensions by the spinning drop method.

Customer benefits

  • Specialized in colloidal samples
  • ISO9001 certification for standard quality control system
  • Highly qualified and continuously trained staff
  • Adapted to customers’ needs

The services provided by the unit are very relevant for product formulation and quality control. Applications include surface and interfacial tension measurements of liquid systems. Also determination of ultra-low interfacial tensions (up to 10-5 mN.m-1) in colloidal liquid-liquid biphasic systems at controlled temperature.

Target customer

Public research organizations, academia and industry in the pharmaceutical, chemical, food and cosmetic sectors.

Additional information

More information can be found at https://www2.iqac.csic.es/qci/

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U12-S06. Surface hydrophobicity characterization

Surface hydrophobicity characterization

For this service we offer a Sigma 701 force tensiometer (Biolin Scientific) with software for control, acquisition and data treatment for the measurement of surface and interfacial tensions. It is equipped with Wilhelmy plate and Du Nouy ring accessories. It can also measure contact angle on powder samples (Washburn method)
We also offer an optical goniometer (Ossila) for measurements of contact angle on flat surfaces.

Customer benefits

  • Specialized in colloidal samples
  • ISO9001 certification for standard quality control system
  • Highly qualified and continuously trained staff
  • Adapted to customers’ needs

The services provided by the unit are very relevant for product formulation and quality control. Applications include surface contact angle determination of liquids on single fibers (fiber diameter greater than 20 mm), solid (cylindrical or plate shapes) and porous materials (cylindrical or plate shapes).

Target customer

Public research organizations, academia and industry in the pharmaceutical, chemical, food and cosmetic sectors.

Additional information

More information can be found at https://www2.iqac.csic.es/qci/

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U12-S07. Evaluation of colloidal stability

Evaluation of colloidal stability

For this service we offer a Turbiscan instrument (Formulaction) for the evaluation of colloidal stability. It measures turbidity by multiple light scattering, as a function of time along the vertical axis by both transmitted and backscattered light. It can analyse samples up to 95 vol% with a wide range of particle sizes (10 nm – 1 mm). The samples are placed inside a temperature-controlled chamber, and the measurements can be carried out from room temperature up to 60 ˚C.

Customer benefits

  • Specialized in colloidal samples
  • ISO9001 certification for standard quality control system
  • Highly qualified and continuously trained staff
  • Adapted to customers’ needs

The services provided by the unit are very relevant for product formulation and quality control.Applications include analysis of colloidal stability of emulsions, suspensions and foams and to determine whether there is sedimentation, creaming, flocculation or coalescence.

Target customer

Public research organizations, academia and industry in the pharmaceutical, chemical, food and cosmetic sectors.

Additional information

More information can be found at https://www2.iqac.csic.es/qci/

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U12-S08. Characterization of materials by high resolution optical microscopy with spectral analysis and scanning electron microscopy

Characterization of materials by high resolution optical microscopy with spectral analysis and scanning electron microscopy

For this service we offer a CytoViva Hyperspectral Imaging System (HSI). The instrument combines enhanced dark field optical microscopy with high resolution spectral imaging. These integrated technologies have been designed to allow optical observation and spectral characterization of nanomaterials and cell matrices. There is no need of sample preparation in advance or fluorescent labelling to observe or characterize spectroscopically nanomaterials in complex media.
We also offer a BX51TRF6 Olympus Optical Microscope that can work with transmitted or reflected light. Different observation methods can be used: bright field, dark field, phase contrast, differential interference contrast, polarized light, and fluorescence. It includes two revolvers to work at short or long distances. Moreover, it is equipped with a digital camera (Olympus DP73) connected to the computer with a software that captures images and videos. A heating stage is available for observations at controlled temperature.

Customer benefits

  • Specialized in colloidal samples
  • ISO9001 certification for standard quality control system
  • Highly qualified and continuously trained staff
  • Adapted to customers’ needs

The services provided by the unit are very relevant for product formulation and quality control.Applications include spectral analysis of nanomaterials, characterization of surfaces and functional groups bound to nanomaterials, spectral characterization of biological samples. Also image analysis of micron-sized emulsions, solid dispersions and liquid crystals.

Target customer

Public research organizations, academia and industry in the pharmaceutical, chemical, food and cosmetic sectors.

Additional information

More information can be found at https://www2.iqac.csic.es/qci/

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U19-S04.

Magistral formulation

The pharmaceutical formulation laboratory is enabled and equipped to store, formulate and reconstitute trial products for differents in vivo preclinical studies with strict quality standards. In addition to drug formulation for preclinical studies and its use in experimental animals. This formulation laboratory equipped to formulate, reconstitute and guarantee the correct storage of the test products used in studies.

Customer benefits

The laboratories include in the unit are certified with ISO-9001 and Good Laboratory Practices (GLP), strict quality standards that allow the production of high-precision results
Also, the studies can be performed under regulatory requirements too, since the performing institution is Certified for Good Laboratory Practices.
Therefore, preclinical studies and safety and efficacy studies in animal models can be carried out in compliance with the strict guidelines of regulatory agencies, ensuring the reliability and traceability of all results and tests carried out in their different services.

Target customer

The services offered in this unit may be of interest to different companies and laboratories that work within the pharmaceutical industry. Companies whose objective is to test possible candidates for molecules, drugs or medical devices. Both in previous legal preclinical studies and animal models of specific pathologies.

References

  1. J Bote, et al. Novel ex-vivo database of a murine model of colorectal cancer using optical coherence tomography. Surg Endosc (2022) 36:S325–S674
  2. V Lucas-Cava, et al. Prostatic artery occlusion: Initial findings on pathophysiological response in a canine prostate model. Translational Andrology and Urology. Transl Androl Urol 2022.
  3. Soria F, et al. Heparin coating in biodegradable ureteral stents does not decrease bacterial colonization-assessment in ureteral stricture endourological treatment in animal model. Transl Androl Urol. 2021 Apr;10(4):1700-1710.
  4. Baez-Díaz C, et al. Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model. Sci Rep. 2020 Apr 28;10(1):7166.
  5. Moreno-Lobato, B, et al. Use of nanomedicine in preclinical wound healing studies. FarmaJournal; Salamanca T 4, N.º 1, (Feb 2019): 178.
  6. Picado Román, N, et al. Drugs most used in experimental animals in a Research Center. FarmaJournal; Salamanca T 4, N.º 1, (Feb 2019): 236.
  7. Moreno-Lobato B, et al. Analytical Validation Study of Hematological Parameters under Good Laboratory Practice Regulations in Different Laboratory Animal Species. Thromb Haemost Res. 2019; 3(1): 1018.
  8. Ballestín A, et al. A Pre-clinical Rat Model for the Study of Ischemia reperfusion Injury in Reconstructive Microsurgery. J Vis Exp. 2019 Nov 8;(153).
  9. R Blázquez , et al. Altered hematological, biochemical and immunological parameters in a porcine myocardial infarction model: predictive biomarkers for the severity of myocardial infarction. Veterinary Immunology and Immunopathology 205 (2018) 49–57.
  10. Vela FJ, et al. Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies. BMC Vet Res. 2017. Apr 7;13(1):93.
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U10-S01. Design & Development of pharmaceutical forms

Design & Development of pharmaceutical forms

Classic parenteral dosage forms: solutions, suspensions, emulsions,…
Parenteral dosage forms for sustained release.
Topical dossage: creams, gels,…
Classic oral dosage forms: capsules, tablets, coated tablets, microgranules,…
Oral dossages forms for suistanable release: hidrophylic matrixes, lipid matrixes, pellets,…

The techniques we use to make the pharmaceutical dosage forms are:

  • binder jet printing,
  • fused deposition modeling (FDM),
  • semi-solid extrusion (SSE),
  • stereolithography

Customer benefits

  • Design of custom and specific formulations with molecules in development phases for preclinical evaluation.
  • 3D printing offers on-demand manufacturing at the point of care with low-cost equipment and one-step processes.
  • Printed personalised medicine

Target customer

  • Pharmaceutical industry (e.g. nutraceuticals, cosmetics, …).
  • Research groups aimed at the development of new drugs and pharmaceutics forms.
  • Printlets: Hospitals, Pharmaceutical Companies and Universities.

Additional information

The following is an example of our bioprinted materials, which were used in the first study on 3D screen printing in the fabrication of drug delivery systems:

Reproduced from International Journal of Pharmaceutics.

Reference: D. Moldenhauer, et al. 3D screen printing – An innovative technology for large-scale manufacturing of pharmaceutical dosage forms. International Journal of Pharmaceutics, Vol. 592, 2021, 120096, ISSN 0378-5173, DOI: 10.1016/j.ijpharm.2020.120096.

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U10-S02. Design & Development of micro- & nanocapsules

Design & Development of micro- & nanocapsules

Design & Development of micro- & nanocapsules for conventional drugs, peptides and proteins.

Customer benefits

Use of micro- and nanotechnologies for the design of specific formulations and capsules with conventional drugs, peptides and proteins for preclinical evaluation.

Target customer

  • Pharmaceutical industry (e.g. nutraceuticals, cosmetics, …).
  • Research groups aimed at the development of new drugs and pharmaceutics forms.
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U10-S03. Design & Development of lipid nanoparticles

Design & Development of lipid nanoparticles

Design & Development of lipid nanoparticles to encapsulate therapeutic actives for drug delivery or gene delivery purposes: SLNs (solid lipid nanoparticles), NLCs (nanostructured lipid carriers), LNPs (self-assembled lipid nanoparticles by microfluidic technology) and niosomes.

Customer benefits

Customized elaboration of nanovehicles to deliver the therapeutic material of interest (mRNA, plasmid DNA, drugs, growth factors, peptides, antibodies…). We are specialists in designing and developing formulations for several therapeutic purposes. Among them, we develop self-assembled lipid nanoparticles, which are formed by fast microfluidic mixing in a NanoAssemblr® platform. These kinds of nanoparticles have emerged as an ideal nanotechnology approach for drug delivery and non-viral gene therapy by the high efficient encapsulation and protection of the therapeutic material from degradation. This microfluidic technology, that has been employed for COVID-19 vaccine, works under GMP conditions and enables reproducibility and scalability, which enhances its clinical translation.

Physicochemical characterization of nanovehicles, following SOPs, regarding mean particle size, polydispersity index and zeta potential. Additional parameters can be determined, such as, pH of nanoparticle suspension, microscopic morphology of the nanoparticles, encapsulation efficiency of the active principle and in vitro release profile. Optionally, biological evaluation can be performed, such as transfection efficiency analysis of non-viral nanovehicles and/or cytotoxicity assays following SOPs that include the ISO 10993-5-2019 Biological evaluation of medical devices.

Target customer

  • Customers with a specific target for therapeutic purposes.
  • Preclinical use for validation in in vitro and in vivo models.

References

  • Gallego I, Villate-Beitia I, Soto-Sánchez C, Menéndez M, Grijalvo S, Eritja R, Martínez-Navarrete G, Humphreys L, López-Méndez T, Puras G, Fernández E, Pedraz JL. Brain Angiogenesis Induced by Nonviral Gene Therapy with Potential Therapeutic Benefits for Central Nervous System Diseases. Mol Pharm. 2020 Jun 1;17(6):1848-1858. doi: 10.1021/acs.molpharmaceut.9b01213.
  • Pastor M, Moreno-Sastre M, Esquisabel A, Sans E, Viñas M, Bachiller D, Asensio VJ, Pozo AD, Gainza E, Pedraz JL. Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm. 2014 Dec 30;477(1-2):485-94. doi: 10.1016/j.ijpharm.2014.10.048.
  • Moreno-Sastre M, Pastor M, Esquisabel A, Sans E, Viñas M, Fleischer A, Palomino E, Bachiller D, Pedraz JL. Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm. 2016 Feb 10;498(1-2):263-73. doi: 10.1016/j.ijpharm.2015.12.028.

Additional information

U10 NP development and characterization.tif

Transmission Electron Microscopy captures of lipid nanoparticles.
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U10-S04. Design & Development of living cells containing microparticules

Design & Development of living cells containing microparticules

Cell encapsulation in alginate based microcapsules.
Optionally, cell viability assays, metabolic activity and other phenotypic / biological studies can be carried out.

Customer benefits

Microencapsulation of cells allows their transplantation in absence of immunosuppression along a wide variety of diseases, with long retention in the engrafted tissue. This strategy improves the engraftment rate and survival of transplanted cells following implantation.

Target customer

Preclinical use for in vivo models

References

  • Ziani K, Espona-Noguera A, Crisóstomo V, Casado JG, Sanchez-Margallo FM, Saenz-Del-Burgo L, Ciriza J, Pedraz JL. Characterization of encapsulated porcine cardiosphere-derived cells embedded in 3D alginate matrices. Int J Pharm. 2021 Apr 15;599:120454. doi: 10.1016/j.ijpharm.2021.120454.
  • Espona-Noguera A, Etxebarria-Elezgarai J, Saenz Del Burgo L, Cañibano-Hernández A, Gurruchaga H, Blanco FJ, Orive G, Hernández RM, Benito-Lopez F, Ciriza J, Basabe-Desmonts L, Pedraz JL. Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets. Int J Pharm. 2019 Apr 5;560:65-77. doi: 10.1016/j.ijpharm.2019.01.058.
  • Cañibano-Hernández A, Saenz Del Burgo L, Espona-Noguera A, Orive G, Hernández RM, Ciriza J, Pedraz JL. Hyaluronic acid enhances cell survival of encapsulated insulin-producing cells in alginate-based microcapsules. Int J Pharm. 2019 Feb 25;557:192-198. doi: 10.1016/j.ijpharm.2018.12.062.

Additional information

10X-Captured-Brightfield-with-DM_RGB_Brightfield-with-DM.jpgMicroencapsulated cardiospheres 10X Captured Brightfield with DM_RGB_Brightfield with DM.

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U9-S05. Generation and control of nanoparticle aerosols

Generation and control of nanoparticle aerosols

This Unit offers the possibility of generating nanoparticle aerosols from a large variety of liquid suspensions or nanosized powders. Our patented technology allows a reliable aerosol generation from any preformed micro or nanoparticle powder. These aerosols with known and reproducible characteristics can then be used in wide variety of applications.
For determining the particle size and concentration in aerosol phase, several nanoparticle aerosol spectrometers are also available. These allow a real-time determination of the concentration of particulate matter in air streams and environments from sizes down to 5 nm.
Also, the Unit is able to identify nanosize matter from aerosols using a reliable, ultrasensitive identification in diverse matrices, based in introducing trace amounts of labels (eg. rare earth oxides or flurorophores).

The following devices are available through this service:

  • Liquid-phase aerosol generators.
  • Nanoparticle aerosol generator from powder samples.
  • Fluidized bed aerosol generator.
  • Scanning Mobility Particle Sizer (Grimm Aerosol) for nanoparticle aerosols from 5 nm to 10 um.
  • Optical Particle Sizer (Grimm Aerosol) for particulate aerosols from 1 um to 400 um.
  • Environmental exposure chamber with controlled nanoparticle concentration.

Customer benefits

This service is able to produce stable and reliable aerosol streams with nanoparticles of a large variety of origins, e.g., on exposure tests with environmental models or for development and validation of methods for sampling and monitoring of airborne matter.

Target customer

Researchers with interests in environmental modelling, nanoparticle aerosol distribution, pharmaceutical companies for aerosolized drug formulations, development of clinical aerosol formulations, testing of respiratory devices and research in filtering units.

Additional information

https://nfp.unizar.es/wp-content/uploads/2019/07/B4-figure1.jpeg SEM and TEM images of the matter captured from the powder aerosol generator

Selected References:

  1. Fast and simple assessment of surface contamination in operations involving nanomaterials. Clemente, A. et al. J. Hazard. Mater. 363, 358-365, (2019)
  2. A Versatile Generator of Nanoparticle Aerosols. A novel tool in Environmental and Occupational Exposure Assessment. Clemente, A., et al., Sci. Total Environ. 625, 978-986, (2018).
  3. Modelling the size distribution in a fluidized bed of nanopowder. Fabre, A. et al. Environ. Sci. Nano, 4 (3), 670-678 (2017).

Patents:

  • Generador de aerosoles nanoparticulados y procedimiento de generación de aerosoles en continuo asociado a dicho generador J. Santamaria, F. Balas, M.P. Lobera, A. Clemente. Patent Appl. Number: PCT/ES2018/070027 Patent holder entity: University of Zaragoza, VITROCELL SYSTEMS GMBH
  • Method for generating an inhalable micro-or nanoparticulate aerosol from a dry-powdered biocompatible material. J. Santamaria, M.P. Lobera, B. Arauzo, F. Balas, A. Clemente, Spanish Patent EP22382574.
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