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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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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-S04. Microfluidics and microwave-assisted production of nanoparticles

Microfluidics and microwave-assisted production of nanoparticles

Conventional batch reactors may suffer from limitations due to the inefficient heat and mass transfer that makes it very difficult to achieve an accurate control on the synthesis conditions. This has a direct effect on key aspects such as reproducibility, selectivity and scalability. In fact, one of the bottlenecks in the development of Nanotechnology lies in the lack of precise synthesis methods capable of a scaled up production.
Continuous flow reactors based on microfluidic principles offer potential solutions to the aforementioned concerns. The exquisite control afforded by microfluidic reactors enables continuous production of nanomaterials with targeted sizes, shapes and composition. Moreover, the combination with microwave reactors can accelerate the stabilization of metastable phase due to the fast and selective heating supplied by this electromagnetic irradiation.

Customer benefits

The customer can benefit from the Unit´s expertise on the design of versatile microfluidic platforms to produce a broad library of nanostructures in a continuous fashion, often with a strong reduction of processing times with respect to the corresponding batch process. The Unit also offers unprecedented flexibility in terms of tuning the reaction atmosphere. Access to microwave reactors to perform fast heating reactions will be another asset to optimize specific synthesis and/or reactions in liquid media.

Target customer

Pharmaceutical companies, material suppliers, research groups pursuing a controlled and potentially scalable production of materials.

Additional information

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Selected References:

  1. R. Quirós-Ovies, et al., Microwave-driven exfoliation of bulk 2H-MoS2 after acetonitrile pre-wetting produces large-area ultrathin flakes with exceptionally high yield, ACS Nano, 17, 5984-93 (2023).
  2. Manno, R., RanjaN, P., Sebastian, V., Mallada, R., Irusta, S., Upendra K. Sharma, U.K., Van der Eycken E.V., Santamaria, J., Continuous Microwave-Assisted Synthesis of Silver Nanoclusters Confined in Mesoporous SBA-15: Application in Alkyne Cyclizations. Chem. Mat. 32, 7, 2874–2883, (2020).
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U9-S03. Characterization of nanoparticles

Characterization of nanoparticles

The unit has access to different advanced characterization equipment including N2 adsorption (ASAP), porosimetry, several chromatography techniques (GC, HPLC, UPLC, GC-MS), Microwave Plasma-Atomic Emission Spectroscopy (MP-AES) for elemental analysis, UV-VIS spectroscopy, DSC, NTA, TPD/TPR and TGA. On the other hand, there is access to magnetic characterization by SQUID and VSM, Raman Spectroscopy (Alpha300R WITEC Raman confocal microscope), Infrared spectroscopy FTIR (Vertex 70 Bruker) and Fluorescence spectrometry (Perkin-Elmer, LS-45). Scanning Electron Microscopes (SEM) (including 3 dual-beam models); Transmission Electron Microscopes (TEM) (including two ultra-high resolution models with aberration corrector lens: TITAN 80-300 y TITAN CUBE 60-300). X-ray Diffractometers (specialized for powdered, low-angle and heating configurations), 2 X-ray Photoemission Spectrophotometers (XPS).

Customer benefits

The customer will be benefit from the expertise of the Unit´s members to carry out a complete characterization of nano and microstructured materials, ranging from polymeric, biological to inorganic compositions, including morphological, chemical, structural, optical, magnetic properties.

Target customer

Companies, material suppliers, pharma laboratories, research laboratories, conservation, medical laboratories.

Additional information

Selected Reference:

N. Miguel-Sancho, G. Martinez, V. Sebastian, A. Malumbres, I. Florea, R. Arenal, M. Carmen Ortega-Liebana, J.L. Hueso, J. Santamaria, Pumping Metallic Nanoparticles with Spatial Precision within Magnetic Mesoporous Platforms: 3D Characterization and Catalytic Application, Acs Applied Materials & Interfaces, 9 (2017) 41529-41536.

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