Bas van Ravensteijn
Bas van Ravensteijn is a tenure track Assistant Professor at the Department of Pharmaceutics, at the Utrecht Institute for Pharmaceutical Sciences (UIPS). He started his scientific career at the Eindhoven University of Technology (TU/e), where he studied Chemical Engineering (2006 – 2011) with a Master in Organic and Polymer Chemistry. After obtaining his M.Sc. degree he moved to the Van `t Hoff Laboratory for Physical & Colloid Chemistry at Utrecht University (UU) to perform his Ph.D. research focused on the synthesis and self-assembly of complex colloidal particles (2011 – 2015).
His postdoctoral life started at the University of California – Santa Barbara (UCSB). Being part of the Materials Research Laboratory and the Mitsubishi Center for Advanced Materials, he developed new synthetic tools for the efficient preparation of well-defined branched polymer architectures and investigated their application as multi-functional lubricant additives. In 2019, he returned to the Netherlands to join the Materials Solutions Department of the Netherlands Organisation for Applied Scientific Research (TNO). Here, he worked on composite materials for thermo-chemical heat storage. In 2020, he transitioned back to academia with the financial help of an individual Marie Skłodowska-Curie fellowship. Working in the Institute for Complex Materials (ICMS) at the TU/e, he used controlled radical polymerizations to steer the assembly of colloidal particles into out-of-equilibrium superstructures.
He joined the Department of Pharmaceutics in 2021 to set up his own research lines in which the worlds of polymer and physical chemistry and pharmaceutical sciences are brought together in pursuit of more robust and effective nanomedicines.
The research of Bas van Ravensteijn focuses on using concepts from polymer and physical chemistry to rationally design, engineering, and synthesize the next generation of nano-pharmaceutics. By attempting to look beyond the molecular complexity in a biologically-relevant way, design rules for drug delivery vehicles and tissue engineering hydrogels can be obtained. These rules serve as input of targeted screening relying on high precision macromolecular synthetic routes.
1) Out-of-equilibrium routes toward drug delivery vehicles
Polymeric nanoparticles have shown great potential as drug delivery vehicles for a wide variety of pharmaceutical cargos. Encapsulating the cargo in such vehicles leads to enhanced drug efficacy by prolonged in vivo circulation times, targeted delivery, controlled drug release, and cargo protection. A vast majority of the polymeric delivery vehicles are based on amphiphilic block-copolymers. These polymers comprise two distinct segments of which one is solvophobic and the other solvophilic. The incompatibility of the solvophobic segments with the dispersing medium drives the assembly of the polymer chains into micellar structures. The solvophobic interior can be used to load non-soluble drugs into the interior of these supra-polymeric constructs. Relying on the modularity and flexibility of today’s polymer chemistry toolbox, the resulting micelles can be tailored for specific drugs and/or targets. However, a persistent bottleneck in the full-scale application of these polymeric nanoparticles is their limited formation efficiency. A potential route to overcome this hurdle it to perform the assembly and block copolymer formation in one single step in highly concentrated systems. These so-called polymerization-induced self-assembly (PISA) routes can yield well-defined micellar structures with controllable morphology at very high yields. By performing detailed studies into the formation mechanism, stability and drug loading ability, we aim to mature the use of PISA for pharmaceutical purposes.
2) Super-selective drug delivery vehicles. How selective can we get?
A long-standing challenge in drug delivery is the selective targeting of sick cells or tissues only. Leaving healthy cells untouched by the often toxic cargo is crucial to prevent adverse side-effects of the supplied treatment. One approach for delivery vehicles to differentiate sick from healthy cells is by looking at the concentration of certain receptors that are expressed on the surface of cells. For many diseases, sick cells overexpress these receptors, providing a possibility for differentiating healthy from sick cells. Recent theoretical models predict that the selectivity of a drug delivery vehicle that needs to dock on receptor coated surfaces is determined by the number of possible binding conformation between the vehicle and the surface. The more binding modes a vehicle has, the higher the probability for binding. From a theoretical perspective, a high number of binding modes and hence sensitivity to the surface receptor concentration, can be realized by using multi-valent drug delivery vehicles with flexible linkers. Optimizing these design parameters can yield to vehicles that basically only bind to sick cells that overexpress the receptors, while healthy cells remain untouched. In this research project, we would like to take these physical chemical design criteria underlying super-selective binding and translate them to pharmaceutically relevant drug delivery systems.
1 Van Ravensteijn, B. G. P., Zerdan, R. B., Hawker, C. J., & Helgeson, M. E. (2021). Role of Architecture on Thermorheological Properties of Poly(alkyl methacrylate)-Based Polymers. Macromolecules, 54(12), 5473-5483. https://doi.org/10.1021/acs.macromol.1c00149
2 Van Ravensteijn, B. G. P., Voets, I. K., Kegel, W. K., & Eelkema, R. (2020). Out-of-Equilibrium Colloidal Assembly Driven by Chemical Reaction Networks. Langmuir, 36(36), 10639-10656. https://doi.org/10.1021/acs.langmuir.0c01763
3 Chang, F., Van Ravensteijn, B. G. P., Lacina, K. S., & Kegel, W. K. (2019). Bifunctional Janus Spheres with Chemically Orthogonal Patches. ACS Macro Letters, 8(6), 714-718. https://doi.org/10.1021/acsmacrolett.9b00193
4 Van Ravensteijn, B. G. P., Bou Zerdan, R., Helgeson, M. E., & Hawker, C. J. (2019). Minimizing Star-Star Coupling in Cu(0)-Mediated Controlled Radical Polymerizations. Macromolecules, 52(2), 601-609. https://doi.org/10.1021/acs.macromol.8b02375
5 Van Ravensteijn, B. G. P., Hendriksen, W. E., Eelkema, R., Van Esch, J. H., & Kegel, W. K. (2017). Fuel-Mediated Transient Clustering of Colloidal Building Blocks. Journal of the American Chemical Society, 139(29), 9763-9766. https://doi.org/10.1021/jacs.7b03263