Chemoenzymatic surface modification of liposomal drug carriers

Thesis by Steffen Wöll – Christian-Albrechts-Universität Kiel

Drug encapsulation into a carrier system aims to refine drug characteristics via three major pathways. Firstly, physico-chemical properties may be improved. This includes improvement of solubility [4] or the prevention of drug degradation during storage and administration [5].

Secondly, pharmacokinetics can be controlled. This includes extension of systemic circulation time by a reduced glomerular filtration in the kidney [6] or prevention of drug metabolism during circulation [7]. Furthermore, prolonged release after local administration may be achieved [8, 9]. A major pharmacokinetic benefit, and key relation towards Paul Ehrlich’s magic bullet, is the prevention of drug distribution in vulnerable healthy tissues [10, 11], and vice versa the option to selectively target the carrier towards disease-affected tissues and cells [12].

Thirdly, pharmacodynamics may be improved. This improvement may in some cases be primarily explained by pharmacokinetic effects [10, 13]. However, especially large, non-permeable drugs require particulate drug delivery systems to cross cell membranes and subsequently exhibit intracellular effects. This is due to the unique interaction of nanoparticles with cells, leading to cellular uptake by active processes including endocytosis, (macro-)pinocytosis and phagocytosis [14]. Prominent examples are nanoparticulate formulated vaccines [15-17] or nucleic acid- loaded vectors utilized in gene therapy [18].

These three principle mechanisms contribute – alone or in combination [13] – to the possibility to improve the efficacy and safety of drugs via encapsulation in carrier systems. Recent decades of research in biomedical nanotechnology resulted in a large selection of such colloidal drug carriers composed of a plethora of materials with different dimensions, shapes and surface varieties [3]. The following work will focus on liposomal drug carriers due to their marked versatility and biocompatibility among the currently available drug delivery systems. Download the full Thesis: dissertation_steffen_woell.pdf