The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

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

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.

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

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

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.

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

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.

Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.

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

In light of climate change, it is crucial to determine whether plant species can adapt to future climates to avoid extinction. Plants adapt to various conditions by altering their functional traits, such as leaf size or photosynthetic rate. Some traits appear linked and vary together between species,…

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

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

Promotor: T. Hankemeier, Co-Promotores: T. Reijmers, L. Coulier

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

Promotor: Prof.dr. B. van de Water

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.

Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous…

Parkinson's disease is the second most common neurodegenerative disease in the world. One of its symptoms is the loss of dopaminergic neurons in the substantia nigra pars compacta.

Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric…

The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main SC lipid classes are ceramides (CER), cholesterol and free fatty acids.

Promotores: J. Jonkers, K.E. de Visser

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.

Promotor: Prof.dr. J. Kuiper

Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the pa…

The research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In the field of atherosclerosis, we showed that the small peptide Lyp-1 can be used as a targeting molecule…

Promotor: B. van de Water

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.

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.

The investigation into the bidirectional communication between the gut and its host is a rapidly growing area of research, attracting considerable attention for its potential to provide crucial insights into health and disease.

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

This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.

Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst

Inflammatory skin diseases such as psoriasis and atopic dermatitis can severely impact both the physical and social aspect of a patient’s life. Aberrant inflammatory responses are thought to be a major causative factor in these disorders, but an abundance of different factors contribute to the development…

Promotor: G.F.A. Kersten, W. Jiskoot, Co-promotor: B. Metz

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.

This thesis investigated miniaturized mass spectrometry (MS)-based analytical methods to address challenges in analyzing biomass-restricted biological samples.

This thesis focuses on enhancing predictions of central nervous system drug exposure using the LeiCNS-PK3.0, a physiologically based pharmacokinetic model.

Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).

Atherosclerosis is the most prominent underlying pathology of cardiovascular disease and an important cause of major adverse cardiovascular events.

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.

According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).

M. Danhof, Co-promotores: J. Freijer, A. Yassen

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.