Division of BioTherapeutics
The Biologics Formulation Group is led by Prof. Wim Jiskoot. A major challenge in the formulation of biopharmaceuticals is to overcome their inherent instability during production, storage, transportation, handling and administration. We are studying underlying mechanisms of degradation of biopharmaceuticals (including therapeutic proteins, vaccines and advanced therapy medicinal products) in both liquid and dried formulations.
We are using a wide variety of analytical techniques to support these studies, including separation (e.g. HPLC, asymmetrical flow field-flow fractionation), spectroscopic (e.g. fluorescence, circular dichroism), light scattering (e.g. dynamic and static light scattering) and particle characterization (e.g. flow imaging microscopy, nanoparticle tracking analysis, resonant mass measurement) techniques.
Another major challenge with biopharmaceuticals is their delivery. In most cases, the size, hydrophilic nature and instability of this class of drugs precludes the oral route as an efficient way to reach target sites. Therefore, biopharmaceuticals are usually administered parenterally via needle injection or infusion. For vaccines, it is clear that the administration route and subsequent targeting to the immune system strongly influence their safety and efficacy. We are exploring methods and formulations to deliver vaccines via the skin and mucosal routes in preclinical models. We use antigen-loaded nanoparticles to target antigens to different compartments of the immune system and to induce the desired type of immune response (e.g. humoral, cellular, tolerogenic), depending on the disease to prevent (e.g. infectious diseases) or to treat (e.g. allergy, atherosclerosis, cancer).
- Nejadnik M.R., Randolph T.W., Volkin D.B., Schöneich C., Carpenter J.F., Crommelin D.J.A. & Jiskoot W. (2018), Postproduction Handling and Administration of Protein Pharmaceuticals and Potential Instability Issues, Journal of Pharmaceutical Sciences107(8): 2013-2019.
- Varypataki E.M., Silva A.L., Barnier-Quer C., Collin N., Ossendorp F. & Jiskoot W. (2016), Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles., Journal of controlled release : official journal of the Controlled Release Society 226: 98-106.
- Silva, A.L., Rosalia, R., Sazak, A., Carstens, M.G., Ossendorp, F., Oostendorp, J., and Jiskoot, W. (2013) Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: low burst release is crucial for efficient CD8+ T cell activation. Eur. J. Pharm. Biopharm. 83: 338-345.
- Filipe, V., Jiskoot, W., Basmeleh, A.H., Halim, A., Schellekens, H., and Brinks, V. (2012) Immunogenicity of different stressed IgG monoclonal antibody formulations in immune tolerant transgenic mice. mAbs 4: 740-752.
- Jiskoot, W., Randolph, T.W., Volkin, D.B., Middaugh, C.R., Schöneich, C., Winter, G., Friess, W., Crommelin, D.J.A., and John F. Carpenter, J.F. (2012) Protein instability and immunogenicity: Roadblocks to clinical application of injectable protein delivery systems for sustained release. J. Pharm. Sci. 101: 946-954.