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Physicochemical Characterization of Nanomedicines

Compressed fluid-based technology platform for biomaterials processing
Dark-Field optical microscope with spectral analysis

Fast-track nanotherapeutics to market with NANBIOSIS – expert characterization studies tailored for nanomedicines ensure rapid regulatory approval.

Scientific Leaders of the project: Jaume Veciana, Nora Ventosa, Jesús Santamaría, José Luis Pedraz & Carlos Rodríguez.

Coordinator of the project: Jaume Veciana

Industrial problem/gap covered

One of the causes that increases the time required to reach the market in nanotherapeuticsis is the preclinical validation. The standard protocols for more traditional drugs are not applicable for nanomedicines, starting with the study of the physicochemical properties of the nanomaterials. NANBIOSIS offers a complete study plan tailored to meet the demands of each nanomedicine product, from the properties of the materials all the way to their precilinal validation. This is developed in collaboration with the user and starting from a set of basic analytical tests to more sophisticated experiments. Also, some of them are available under GLP for regulatory pruposes.

Description

We offer a complete Physicochemical Characterization. e.g., size distribution, composition, purity, surface characteristics, stability, and more adapted to the different products by using the most sophisticated equipment and taking advantage of the expertise of scientist internationally recognized in the matter. 

Services involved: Standar services

  • Size of Nanoparticles (NP)by:
    • Atomic Force Microscopy (U6, U9, & U10)
    • Transmission Electron Microscopy (U6 & U9)
    • Electrospray Differential Mobility Analysis (U6 & U9)
    • High-Resolution Scanning Electron Microscopy (U6 & U9)
    • DLS y MALS (Size, Size Distribution)(U12)
    • X-ray diffraction (solid NP) (U10)
  • Measuring NP aggregation propensities with DLS (U6, U9 & U12)
  • Zeta Potential (U6, U9, U10 & U12)
  • pH of NP Suspensions (U6, U9, U10 & U12)
  • Lipid composition (U6)
  • Determination of Metallic NPs in Blood or in Rat Tissue with Inductively Coupled Plasma-Mass Spectrometry(ICP-MS) (U9)
  • Quantification of Free and Chelated Gadolinium Species in Nanoemulsion-Based MRI Contrast Agent Formulations using Hyphenated Chromatography Methods (U6)
  • LC/MS/MS and Free vs. encapsulated drug under either GLP (U10) or non-GLP (U6 & U9)
  • Stability of the active or the final pharmaceutical form (according to ICH) under either GLP or non-GLP (U10)
  • Solubility profiles of the final pharmaceutical formunder either GLP or non-GLP (U10)

Others

  • Concentration, charge & Size of Flourescent NP by NanotrackingParticle Analysis (U6)
  • Optical Analysis by Nano-scale Optical Microscope: Dark-Field optical microscope with spectral analysis (U12)
  • Size of particles in formulations for pulmonary delivery (aerosols and nebulized) (U10)
  • Determination of aerodynamic size (U10)
  • Surface Functional groups by ATR (U6 & U9)
  • Surface Organic material in metallic NP by TGA (U9)
  • Accessible surface charge of NP and size pore (BET) (U9)
  • Composition by XPS (U9)
  • Biomolecule-NP interaction by ITC (U6)
  • Density of solids by pycnometer (U6)
  • Size & morphology of concentrated systems by 3D DLS & SLS multiangle (MALS) (U12)
  • Rheology (viscosity, shear-thinning, shear thickening, elastic and viscous modulus, relaxation times,etc) (U12)
  • Refraction index and density of liquids (U12)
  • Critical micellar concentration, surface and interfacial tension of pure liquids, solutions and colloidal dispersion (U12)
  • Structural determination by SAXS (U12)
 

Some examples are described in the following publications:

  • Ferulic acid-loaded polymeric nanoparticles prepared from nano-emulsion templates facilitate internalisation across the blood–brain barrier in model membranes, L. Garcia, S. Palma-Florez, V. Espinosa, F. Soleimani Rokni, A. Lagunas, M. Mir, M. J. García-Celma, J. Samitier, C. Rodríguez-Abreu and S. Grijalvo. Nanoscale, 2023, 15, 7929–7944 DOI: 10.1039/d2nr07256d
  • Stable nanovesicles formed by intrinsically planar bilayers. Mariana Köber, Sílvia Illa-Tuset, Lidia Ferrer-Tasies, Evelyn Moreno-Calvo, Witold I Tatkiewicz, Natascia Grimaldi, David Piña, Alejandro Pérez Pérez, Vega Lloveras, José Vidal-Gancedo, Donatella Bulone, Imma Ratera, Jan Skov Pedersen, Dganit Danino, Jaume Veciana, Jordi Faraudo, Nora Ventosa J Colloid Interface Sci. 2023 Feb;631(Pt A):202-211. DOI: 10.1016/j.jcis.2022.10.104.
  • Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage Regeneration. Lafuente-Merchan M, Ruiz-Alonso S, Zabala A, Gálvez-Martín P, Marchal JA, Vázquez-Lasa B, Gallego I, Saenz-Del-Burgo L, Pedraz JL.  Macromol Biosci. 2022 Mar;22(3):e2100435. doi: 10.1002/mabi.202100435. Epub 2022 Jan 22. PMID: 35029035.
  • Correlation between Biophysical Properties of Niosomes Elaborated with Chloroquine and Different Tensioactives and Their Transfection Efficiency. Sainz-Ramos M, Villate-Beitia I, Gallego I, Al Qtaish N, Menéndez M, Lagartera L, Grijalvo S, Eritja R, Puras G, Pedraz JL. Pharmaceutics. 2021 Oct 26;13(11):1787. doi: 10.3390/pharmaceutics13111787. PMID: 34834203; PMCID: PMC8623750
  • MKC-Quatsomes: a stable nanovesicle platform for bio-imaging and drug-delivery applications. Guillem Vargas-Nadal, Mónica Muñoz-Úbeda, Patricia Álamo, Montserrat Mitjans, Virtudes Céspedes, Mariana Köber, Elisabet González-Mira, Lidia Ferrer-Tasies, Maria Pilar Vinardell, Ramón Mangues, Jaume Veciana, Nora Ventosa Nanomedicine 2020 Feb:24:102136. DOI: 10.1016/j.nano.2019.102136
  • Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis, M. Moreno-Sastre, M. Pastor, A. Esquisabel, E. Sans, M. Viñas, A. Fleischer, E. Palomino, D. Bachiller, J. L. Pedraz. International Journal of Pharmaceutics 498 (2016) 263–273.
  • Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic Fibrosis. M. Moreno-Sastre, M. Pastor, A. Esquisabel, E. Sans, M. Viñas, A, D. Bachiller, V.J. Asensio, Á. Del Pozo, E. Gainza and J. L. Pedraz. International Journal of Pharmaceutics 477 (2014) 485–494
  • α-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration. I. Cabrera, I. Abasolo, J. L. Corchero, E. Elizondo, P. Rivera Gil, E. Moreno, J. Faraudo, S. Sala, D. Bueno, E. González-Mira, M. Rivas, M. Melgarejo, D.Pulido, F. Albericio, M. Royo, A.Villaverde, M.F. García-Parajo, S. Schwartz Jr., N. Ventosa,* and Jaume Veciana* Adv. Healthcare Mater. 2016, DOI: 10.1002/adhm.201500746
  • Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents. I. Cabrera, E. Elizondo, O. Esteban, J. L. Corchero, M. Melgarejo, D. Pulido, A. Córdoba, E. Moreno, U. Unzueta, E. Vazquez, I. Abasolo, S. Schwartz, Jr., A. Villaverde, F. Albericio, M. Royo, M. F. García-Parajo, N. Ventosa, and J. Veciana. Nano Letters 2013 13 (8), 3766-3774. DOI: 10.1021/nl4017072

U6. Dynamic light scattering for particle size and Z potential measurements.

U10. Dissolution_rate_determination_equipment

U12-E02. CytoViva Hyperspectral Imaging System (HSI).

Our Unit 6 is located at the Instituto de Ciencia de Materiales de Barcelona (ICMAB-CSIC), in Barcelona, and under the coordination of Professor Jaume Veciana and Prof. Nora Ventosa, current directors of NANOMOL Group, which is a research group with wide expertise and recognized excellence in the synthesis, processing and study of molecular and polymeric materials with chemical, electronic, magnetic and biomedical properties.  It gathers several laboratories, perfectly equipped, to perform the mission of this facility: the development, characterization, and large-scale production of molecular biomaterials of therapeutic or biomedical interest, with controlled micro-, nano- and supramolecular structure. One example of Key-Enabling-Technology (KET) available in this unit is a simple one-step methodology, DELOS-SUSP, based on the use of compressed fluids (CF), such as CO2, to prepare particulate materials with precise and reproducible structural characteristics at micro-, nano- and supramolecular levels (size, shape, internal structural gradients, supra­molecular organization and crystalline purity). This example shows one of the singularities of this unit is that counts with CF–based plants at different scales, from mL to L, which allow process development by QbD and process scale-up.

 
 
The NANBIOSIS Unit 6 is works under the ISO9001 certification for standard quality control system

Unit 9, integrated in the Nanostructured Films and Particles Group at the Institute of Nanoscience of Aragón (INA) coordinated by Dr. Jesús Santamaría, has as objective the synthesis of nanoparticles with applications in biomedicine. The unit provides an automated system for the synthesis of nanoparticles using laser-induced pyrolysis of chemical precursors in gas and/or aerosol phase, which enable either individual nanoparticles or biocompatible hybrid nanostructures to be produced in large quantities. In addition, this facility is able to draw on a wide range of nanoparticles fabrication technique, as well as having the necessary specialized personnel, to undertake exhaustive characterization of the microstructure, chemical composition, particles size and distribution of sizes, as well as magnetic, optical and colloidal properties and degree of biological functionality of the synthesized material.

Located at the Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Campus of Alava in Vitoria. Our Unit 10 is led by Prof. José Luis Pedraz and consists of large laboratories for cell culture, chromatography equipment, sample preparation and characterization, and one specific for scale preparation of pharmaceutical formulations. Recently the group has incorporated 3D bioprinters of the last generation with different technologies based on extrusion, inkjet, among others. It has also incorporated self-assembly equipment of nanoparticles based on microfluidic technologies.

This Unit can design and evaluate dosage forms both classical and new dosage forms of biotech drugs, DNA, RNA, and vaccines using different methodologies based on micro and nano-medicine and the latter technology based on the microencapsulation of cells, peptides, proteins, and in general of biotech products, as well as the development and design of non-viral vectors for gene therapy, is one of the biggest singularities of this Unit. It counts on the most advanced equipment for micro and nanoencapsulation.

The Unit aims to determine experimentally all the variables needed to develop an optimal formulation and work instructions for preparing final pharmaceutical products.

The pharmaceutical technology applied to drug development involves the selection of materials and procedures that can be adapted to different processes that lead to specific pharmaceutical forms. To do that, the Unit10 counts with the most advanced equipment to cover the development for all the steps of the process.

One of the singularities of this Units is that is GLP certified by the Spanish Medicament Agency

Our Unit 12 is located at the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), in Barcelona and it is coordinated by the Colloidal and Interfacial Chemistry Group, led by Dr. Carlos Rodríguez. The unit is focused on the characterization of nanostructures in liquids and liquid/liquid interfaces, such as micelles, liposomes, micro- and nano-emulsions, and nanoparticles. The unit features state-of-the-art instrumentation for the determination of various parameters such as size distribution and zeta potential (surface charge), critical micelle concentration (CMC), solubilization capacity, osmolarity, surface and interfacial tension, wettability, refractive index, turbidity, colloidal stability, density, viscosity and other rheological parameters (shear and elastic moduli, critical yield stress, etc.)

The Unit 12 has implemented and maintains the ISO9001 certification forstandard quality control system.