In this book liposomes are explored as delivery system for allergen-specific immunotherapy. Both cationic and anionic formulations are prepared with Bet v 1, one of the allergens in birch pollen.

Promotores: Wim Jiskoot; Ferry Ossendorp

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.

Membrane fusion is a vital process in living organisms and is mediated by zipper-like proteins.

Is there a sufficiently large market for drug screening and testing in Zebrafish larvae using membrane fusion?

Metal-containing molecules combine geometrical features and a reactivity that are inherently different from that of organic molecules. My research focuses on light-activatable metal-based anticancer drugs and metal-functionalized liposomes. Light is a very selective way to activate photosensitive drugs…

Promotor: E. Bouwman, Co-promotor: S. Bonnet

Liposomes hold great promise for peptide-based personalized cancer vaccination, especially when administered intradermally. However, current liposome preparation methods are very time consuming (resulting in long development times per formulation), whereas personalized cancer vaccination requires very…

Promotores: Prof.dr. J. A. Bouwstra, Prof.dr. W. Jiskoot

Vaccination via the skin or the mucosae

Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

Glucocorticoids (GCs) are widely prescribed as anti-inflammatory drugs due to their well-established immunosuppressive effects.

For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated…

Main challenges in skin vaccination are overcoming the stratum corneum (SC) barrier and targeting the antigen presenting cells (APC) in the epidermis and the dermis.

Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination.

The potential of liposomal cancer vaccines

The Delivery of Biotherapeutics research group is led by Prof. Matthias Barz and focusses on the synthesis and characterization of polypept(o)ids and their application in nanomedicine to improve existing therapies or enable novel diagnostic or therapeutic approaches.

In the near future oral polio vaccine (OPV) will be replaced by inactivated polio vaccine (IPV) as part of the eradication program of polio. For that reason, there is a need for substantial amount of safe and more affordable IPV for low-income countries. Bioneedles, which are biodegradable mini-implants,…

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based…

In this thesis, we will utilize embryonic zebrafish tumour models to understand the interaction between engrafted human cancer cells and macrophages from the host, test drug administration modalities and anti-cancer efficacies of newly-developed PDT and PACT compounds, and test a light-triggered liposomal…

Promotoren: G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Science, Institute of Biology Leiden (IBL)

Promotores: W. Jiskoot, F. Ossendorp

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery.

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: A. Kros

This thesis describes the development of improved formulations and alternative delivery strategies for polio vaccination.

Promotor: A. Kros

Promotor: E. Bouwman, Co-promotor: S. Bonnet

Liposomes – nano-sized spheres composed of fatty molecules – are very promising for vaccination. Bio-pharmaceutical scientist Naomi Benne discovered that the immune response in animal models can be steered by varying the charge of the liposomes. She obtained her PhD degree on 8 September for this research,…

PhD Defence

The group of Dr. Roxanne Kieltyka designs and synthesizes molecules that self-assemble into polymeric materials using specific non-covalent interactions. These substrates can be used for numerous applications in medicine ranging from disease detection to cell delivery depending on the (bio)molecular…

CONCLUSION: This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our observation that the induction of macrophage anti-tumor activity by L-MTP-PE required IFN-gamma may be of relevance for the optimization of L-MTP-PE therapy in…

Exploring the mechanism of targeted nanoparticle-mediated drug delivery using the zebrafish model

The aim of the project is the development of polypept(o)ide-based delivery systems to use siRNA as systemic applicated therapeutic agent against e.g. solid tumors

Alexander Kros and co-workers describe how mesoporous silica nanoparticles (MSNs) are delivered into cells via membrane fusion thereby omitting endocytosis pathways. Fusion is induced by a pair of complementary coiled-coil lipopeptides inserted into the membrane of cells and in the bilayer of lipid-coated…

The RNA guided endonuclease based on the CRISPR/Cas system of Streptococcus pyogenus is a potent new tool for genome engineering in plants.

Promotor: E. Bouwman, Co-promotor: S. Bonnet

Petra van der Bekerom, Joris van der Voet, and Johan Christensen, three assistant professors at Leiden University, conducted a large-scale survey experiment about whether citizens are more negative about failing service delivery than private organizations.

PURPOSE: To determine the effect of elasticity on the skin permeation of ketoprofen from surfactant-based vesicular formulations and elastic liposomes.

Data science offers exciting new instruments for governments to reach out to citizens, for example by using data-driven information channels, providing real-time simulations, or personalizing services based on citizen data. At the same time, the possibilities and use of data science methods can have…

Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC.

Dit proefschrift beschrijft een collectie aan alternatieve strategieën voor het begrijpen, ontwerpen en toepassen van lipide nanosystemen, waarin de rol van de bio-nano interacties centraal staan. In het bijzonder wordt gekeken naar de interactie van RNA-lipide nanosystemen, bekend van de toepassing…

The work described in this dissertation contributes to a better mechanistic understanding of nanoparticles in vivo. To achieve that goal, we used the zebrafish as a highly predictive pre-screening model of nanoparticles.

Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles.

A structural investigation of coiled coil peptides used as membrane fusogens, mimicing naturally occuring coiled-coil fusion proteins. Synthetic modifications have been made to alter lipid attachment, secondary structure and to insert photoactive azobenzene moieties for active control over coiled coil…

This book describes the different approaches for drug delivery to the brain with an emphasis on the physiology of the blood-brain barrier (BBB) and the governing principles and concepts for drug delivery across the BBB

The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the…

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…