This thesis focuses on the application of lipid-based nanomedicine in drug delivery, including small molecular antitumor drugs and biomacromolecules including mRNA, and evaluates their biological performance.

Promotor: A. Kros

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

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…

The polypept(o)ide hybrid material attracted more and more attention over the past decade by combining the multifunctional characteristics of polypeptides with the shielding characteristics of polypeptoid-pSar possessing similar properties as a shielding material as polvethylene glycol(PEG). Polysarcosine…

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

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 intradermal administration route is attractive for vaccine delivery, because of the highly populated antigen-presenting cells in the skin. However, the skin’s main physical barrier, the stratum corneum, prevents vaccines from entering the skin.

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

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

Promotor: A. Kros

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

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…

Vaccination via the skin or the mucosae

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.

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.

This thesis describes the design, characterization and application of dextran based crosslinked network.

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,…

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

On Monday 22 April, Dr. Crystal Ennis, Dr. Shivant Jhagroe, and Dr. Yujing Tan will presented the progress of their Seed Grant project 'Governing Delivery Platform Companies'. This project examines the interaction between platform companies, local authorities, workers, and households to understand the…

How does the social infrastructure affect administrative burdens associated with digital government services? The paper 'Administrative burden in digital public service delivery: The social infrastructure of library programs for e-inclusion' published in the Review of Policy Research by Sarah Giest…

There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. Leiden University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP)…

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.

In dermatology, there should be a high level of multidisciplinary collaboration among institutes and specialists, Professor of Translational Dermatology, Robert Rissmann, will say in his inaugural lecture on 8 July. He is building an infrastructure that will put pre-clinical and clinical skin research…

In the Drug Research theme, we primarily work with rodents. Rodents, such as mice, are one of the most common laboratory animals. These small mammals are easily housed and exhibit a rapid rate of reproduction.

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.

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

Is is possible to better predict the validity of drug candidates?

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.

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.

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

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

The drug discovery pipeline is used to describe the stages in drug discovery. The earliest stage concerns with the identification of potential targets and molecules ('hits') that can modulate their function, while more advanced stages are about developing these hits into viable experimental drugs and…

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics.

Citizens in multiple crime-ridden countries strongly support the militarization of security—that is, placing the military in charge of traditional policing duties. Yet, we know little about the determinants of such support. Do people approve of militarization even in the face of human fatalities? Political…

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

Research in this group, headed by Gerard van Westen, focusses on computational methods integrated in different parts of the drug discovery process. More specifically, topics include innovative treatments for cancer, selectivity modeling, translational research, allosteric modulation, drug resistance…

In this research group, headed by Prof. Erik Danen, the aim is to unravel cellular signaling mechanisms in normal and diseased cells, with a long-standing interest in cell adhesion signaling. In complex multicellular organisms such as ourselves, a division of labor emerges where different tissues and…

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.