Both our knowledge and comprehension of processes linked to circumstances of chronic inflammation has been improved decisively by discovering and characterising a respectable number of involved inflammation receptors and inflammation mediators. One crucial milestone in this development has been placed by identifying selectins as a family of adhesion receptors, which mediate for initial contact between leucocytes and vascular endothel in inflamed areas. This, however, allows a cascade of complex leucocytical adhesion as well as migration. Since they hold a rather central and initial position within inflammation affairs as such, both the vascular selectines E and P embody ideal target structures for focussedly enriching anti-inflammatory medication within inflamed tissue. Furthermore are they only locally distributed on conditions of inflammation exclusively. The aim my work had been going for was to investigate the suitability of vascular selectins as molecular target structures for enrichment of immuno-liposomes at inflamed vascular endothel. As a general principle, this could - in case of success - possibly be a new strategy in carrying out anti-inflammation therapies. In a primary part of the project I have prepared E-selectin-directed immuno-liposomes as transportation vehicles for drugs. My being able to both develop and characterise a totally new antibody-linking method for creation of long-circulating immuno-liposomes with PEG-terminal antibody binding without the necessity of protein derivation has to be seen as tightly connected to this. During the in-vitro-targeting checkup that followed thereafter, specific enrichment of liposomes with anti-E-selectin antibodies has been achieved. In order to have my in-vitro-tests come closer to real physiologic conditions in continuously run-through blood-vessels, especially postcapillary venoles, I have complemented targeting checkups in static conditions with further experiments which I had carried out in simulated shear force conditions as they exist in capillary vessels. For the tests mentioned above, I have used a special flowing-through-simulation apparatus that had been self-developed within the team. I was able to show that - even in these dynamic conditions - specifically functionalised immuno-liposomes bind in fact more frequently than either unfunctionalised or unspecifically functionalised referential liposomes. As a final issue, the potential ability of human vascular endothel cells of internalising liposomes was analysed. Hereby I was able to prove intra-cellular location of vesicles by means of several different techniques. To eventually sum it all up I can determine that vascular selectines embody reasonably attractive and suitable molecular target structures for enriching immuno-liposomes at vascular endothel. By targeting them, it is in inflammation conditions possible to somehow focussedly and specificly transport antiinflammatory drugs directly like glucocorticoids into the very scene of action. Since selectines are distributed within the inflamed area exclusively, parallel negative influence on intact tissue as well as possible hazards of inducting unwanted side effects can be reduced down to a tolerable dimension. |