Viola Tokárová – PhD thesis summary

Investigation of targeted particle adhesion to biological and non-biological substrates

The presented dissertation deals with the preparation and characterization of various types of nano- and micro-particles with a possible application in the pharmaceutical industry for targeted delivery of active substances. Adhesive properties of the particles are essential knowledge in targeted delivery and therefore a purpose designed adhesion cell was developed, which is used in particle adhesion determination to a certain type of the substrate. The first types of studied particles were composite polymer microparticles based on a temperature-sensitive polymer PNIPAM. As a part of the composite structure the use of iron oxides nanoparticles was applied with the ability to dissipate heat due to external radio-frequency field. The influence of the external pulse changes on the structure and thus the size of the particles was investigated, as this can control the release kinetics from the particles on demand. The adhesion of these particles inside the adhesion cell on different types of substrates was then studied, and the rate of adhesion was evaluated in terms of substrates hydrophobicity and also as the influence of temperature and particle structure changes.

The next part of the thesis describes the preparation and characterization of silica nanoparticles with covalently bound antibody on their surface. For adhesion experiments the specific binding of an antibody to an antigen was used. In our case, the antibody called M75 was chosen which specifically binds to an antigen CA IX (carbonic anhydrase 9), which is generated in the proliferation process of tumor cells. The specific interaction of M75-CA IX could be then used as biomarker of tumor region but also for direct delivery of an active agent in the cancer treatment. The adhesion of M75-modified particles to an antigen CA IX but also on tumor cells was studied. The next part of the thesis has followed the previous chapter, in which the antibody-modified silica nanoparticles were enriched by the iron oxide nanoparticles as a contrast agent for further adhesion study of the particles by magnetic resonance imaging. The first in vivo experiments on laboratory nude mice were carried out and the suitability of the particles for the subsequent adhesion tests of tumor proliferation was shown. The last part describes the preparation of composite microcarriers with an antibacterial effect. The particles were prepared by the spray drying method with size distribution of a few microns. The body of the particles was made of a biocompatible and biodegradable polysaccharide chitosan and antibacterial component was formed by the silver nanoparticles. The bioadhesion character of composite microcarriers to different strains of bacteria was tested with subsequent diffusion and penetration of the silver nanoparticles. The so-prepared particles could be used in targeted drug delivery, e.g. with nasal application or in the open wounds treatment.