Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

Source: Eur J Med Chem, Volume 101, pp. 681-91 (2015)

PURPOSE: In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products.

Promotor: J.A. Bouwstra Co-promotor: A. El Ghalbzouri

Dissolving microneedles are a subgroup of microneedle types that completely dissolve within the skin. During this dissolving process the vaccine, stored in the needle matrix, is released into the skin.

Prematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are not necessarily similar to prematurely born neonates.

The progressive loss and degeneration of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). The onset and progression of PD can be triggered by multiple risk factors, for instance, genetic mutation, environmental exposure, and aging.

The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondri…

Lipid formulations have demonstrated strong potential for nucleic acid delivery,particularly with the success of COVID-19 vaccines. Despite these advances, manyaspects of lipid formulations remain unclear.

Vaccination via the skin or the mucosae

Promotor: W. Jiskoot, Co-promotor: A. Hawe

It is the aim of this project to better understand how the physical properties of lipids influences the structure and overall barrier function of the skin.

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

Promotor: Prof.dr. J.A. Bouwstra, Co-promotor: Dr. A. El Ghalbzouri

The zebrafish is a promising vertebrate model organism in early drug discovery and development.

The chemical and structural heterogeneity of toxoid vaccines makes their analysis challenging. However, detailed insights on a molecular level can be obtained by mass spectrometry.

Promotor: Prof.dr. M. Danhof, Co-promotor: O.E. Della Pasqua

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye.

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

Immunotherapies for cancer are an emerging class of therapeutic strategies which aim to treat cancer via augmentation of the immune system.

The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.

Bet v1, the major allergen in birch pollen, is one of the main causes of allergies such as asthma and rhino-conjunctivitis. Additionally it is the main cause of birch pollen allergy in humans.

The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market.

This paper describes two synthetic lipid models designed to replace human stratum corneum (SC) in studies of the impact of volatile organic chemicals on the molecular organization of the skin barrier lipids.

There is considerable need for improved skin models to develop safe and efficient drugs for skin delivery as well as for cosmetic and chemical product testing on the skin.

PURPOSE: The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination.

Heart failure is a major health care problem with high mortality.

Promotor: Prof.dr. A. P. IJzerman, Co-Promotor: Dr. L.H. Heitman

Our in-house human skin equivalents contain all stratum corneum (SC) barrier lipid classes, but have a reduced level of free fatty acids (FAs), of which a part is mono-unsaturated. These differences lead to an altered SC lipid organization and thereby a reduced barrier function compared to human skin.…

Developing new medicines is one of modern science's most significant hurdles, a process marked by high costs, long timelines, and frequent failures of promising candidates.

Promotor: Prof.dr. T. Hankemeier, Co-Promotor: R.J. Vreeken

Promotores: Wim Jiskoot; Ferry Ossendorp

Promotor: Prof.dr. T. Hankemeier, Co-promotor: T.H. Reijmers

The potential of bioneedles to deliver influenza vaccines was investigated.

This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis.

With our research and teaching, we help make the world a better place. We join in the academic and public debate, and seek answers to economic and social issues – not just at the local and regional level but at the global one too.

Accelerating the diagnosis and personalising the management of inherited metabolic diseases.

Promotor: Prof.dr. T. Hankemeier, Co-promotores: Heiko van der Linden, Paul Vulto

Promotors: W. Jiskoot; G.J. Witkamp, Co-promotor: M.R. Nejadnik

Atherosclerosis, in particular rupture of atherosclerotic plaques, is the underlying cause of most heart attacks or strokes and is the leading cause of death worldwide.

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Promotor: Prof.dr. B. van de Water, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis

Cardiovascular diseases are a leading cause of death worldwide, and better models are urgently needed for disease progression studies and drug development.

Animal models suggest that the chemokine ligand 2/CC-chemokine receptor 2 (CCL2/CCR2) axis plays an important role in the development of inflammatory diseases. However, CCR2 antagonists have failed in clinical trials because of a lack of efficacy.

A main goal of MSBB research is to address the major bottle-necks in combatting viral diseases: the lack of experimental models that are representative of human pathology and are cost effective and versatile. Viral diseases such as those that cause viral hemorrhagic syndromes or severe acute respiratory…

Leiden University research institutes based in Leiden and The Hague.

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects…