Robbert Jan Kok
Drug Delivery Technology
Robbert Jan Kok is Professor Drug Delivery Technology in the Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS). He is an expert in the novel delivery approaches and biopharmaceutical evaluation of nanomedicines. Prof. Kok obtained his Pharmacy degree (1992) and PhD (1998) at Groningen University. The subject of his PhD research was drug targeting to the kidney. In subsequent projects he studied the targeted delivery of drugs to endothelial cells in inflammation and cancer; to liver and kidney cells in fibrosis; to tumor cells. He also studied polymeric delivery systems for local delivery of anti-inflammatiory and vasculature-enhancing drugs. He joined Utrecht University as Assistant Professor in 2006 and became Associate Professor in 2009. He is the current Director of the bachelor programme in Pharmacy and Director of Education of the Department of Pharmaceutical Sciences.
Research in the Kok group is dedicated to improving the four ADME aspects of pharmacokinetics (Availability, Distribution and Metabolism/Elimination) by incorporation of drug molecules in innovative delivery systems. Research projects in his group are related to oral drug delivery or to parenteral drug delivery strategies.
Oral drug delivery
Novel manufacturing technologies allow for individualized production of medication with tailored drug doses or release profiles. We compare different approaches such as 2D- and 3D printing, formulation of drugs in amorphous solid dosage forms and encapsulation of drugs in polymeric particles.
People involved: Tamanna Lashkari, Levent Kocabas, Sejad Ayyoubi (Erasmus MC)
Parenteral drug delivery
Organs like liver and kidney express transporter proteins that are involved in the clearance of endogenous and exogenous compounds. These clearance pathways can also be exploited for intracellular delivery of drugs. A wide range of “nanocarrier” systems is at hand to achieve cell-specific targeting, ranging from drug-peptide conjugates to lipid- and polymer-based nanoparticles. Biopharmaceutical and pharmacological aspects are carefully considered in the selection of the drug-nanocarrier combination, aiming for efficient accumulation of the drug in target cells and avoidance of cells/tissue that are at risk for unwanted side effects. Once in vitro proof-of-concept is obtained, biopharmaceutical and preclinical evaluation in animal models demonstrate the improved therapeutic index of nanomedicine based drugs.
People involved: Yi Yang (Pharmacology group UIPS)
In a different approach, one can achieve sustained drug levels at therapeutic target sites using injectable or implantable depot formulations. Currently, we investigate polymeric microspheres and (lyophilized) hydrogels for this purpose.
People involved: Tamanna Lashkari
Completed PhD projects (UU-only)
- Design of kidney-targeted drug-carrier conjugates for the inhibition of profibrotic signaling cascades (Emmy Dolman)
- Pharmacokinetics of connective tissue growth factor: implications for its use as biomarker (Karin Gerritsen)
- Targeted inhibition of tumor growth and angiogenesis (Roy van der Meel)
- Investigation of nanobody-decorated albumin nanoparticles for tumor targeting (Isil Altintas)
- Polymeric microspheres for local delivery of proteins by administration under the kidney capsule (Filis Kazazi)
- Polymeric particles for sustained and local drug delivery (Farshad Ramazani)
- Drug-eluting stent coatings for the treatment of bronchotracheal cancer (Louan Chen)
- Liposomal and polymeric nanoparticles for targeted delivery of hydrophobic and hydrophilic drugs (Shima Gholizadeh)
- Lipid-based nanocarriers for the delivery of biotherapeutics (Maria de Matos)
- Drug conjugates and polymeric micelles for targeted delivery of kinase inhibitors (Haili Shi)
- Vascularization of diabetes-reversingimplants: Development of sustained release formulations of proangiogenic growth factors (Karina Scheiner)
- Scheiner K et al, Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b- Poly(l-lactide) Multiblock Copolymer Microspheres. ACS Omega. 2019 Jul 1;4(7):11481-11492.
- Falke LL et al. Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres. Biomaterials. 2015 Feb;42:151-160.
- Shi H et al. Folate decorated polymeric micelles for targeted delivery of the kinase inhibitor dactolisib to cancer cells. Int J Pharm. 2020 May 30;582:119305.
- de MAtos MBC et al. Thermosensitive liposomes for triggered release of cytotoxic proteins. Eur J Pharm Biopharm. 2018 Nov;132:211-221.
- Dolman ME et al. Drug targeting to the kidney: Advances in the active targeting of therapeutics to proximal tubular cells. Adv Drug Deliv Rev. 2010 Nov 30;62(14):1344-1357.