Entwicklung einer antibakteriell beschichteten Harnleiterschiene

Die vorliegende Arbeit beschäftigt sich mit der Entwicklung einer antibakteriell beschichteten Harnleiterschiene. Dies soll dazu dienen, Komplikationen im Zusammenhang mit der Bildung von Biofilmen zu vermeiden oder zu verringern. Aus einer Auswahl verschiedener antibakteriell wirksamer Arzneistoff...

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Bibliographische Detailangaben
1. Verfasser: Belz, Elvira
Beteiligte: Keusgen, Michael (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Veröffentlicht: Philipps-Universität Marburg 2009
Pharmazeutische Chemie
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Inhaltsangabe: The work at hand deals with the development of an ureter stent coated with an antibacterial agent. This coating is meant to prevent or reduce biofilm-related complications. Ethacridine lactate was chosen as best alternative out of a variety of some antibacterial agents. This decision was based on a Spectral Phase Interference (SPI) analysis, which is a method for monitoring binding events on a solid surface in real time. Two immobilization strategies were investigated. Following the SPI results, a direct immobilization inside the material of the stents (made of polyurethane) was chosen rather than immobilization via spacers, for higher amounts of ethacridine lactate could be applicated this way. Ethacridine lactate was immobilized by soaking the polymer in solvents containing the agent. During the drying process, ethacridine lactate was embedded into the matrix. Success was evaluated by release experiments. Released amounts of ethacridine lactate were at first measured by photometry (UV/Vis) and later by fluorescence spectroscopy. The higher sensitivity of fluorescence spectroscopy yielded many advantages. According to release experiments, the most suitable solvents for soaking were ethanol and methanol. Because of the lower toxicity ethanol was chosen as the soaking solvent for the following works. Different coatings of amorphous carbon were investigated with regard to their release properties. No differences between the coatings were found. From uncoated stents, slightly lower amounts of ethacridine lactate were released, compared to coated stents. This was only observed on samples with very low release rates. By further release experiments, it was shown that stents containing ethacridine lactate could be stored in the dark for at least three months. On the other hand, UV light destroys ethacridine lactate. Release profiles of samples which were sterilized by ethylene oxide were shown not to be worse than those of the unsterilized samples. To prove the efficacy of the modified stents a microbiological assay was developed. It is based on the assumption that from samples with bacteriophobic surface more microorganisms are washed into a rinsing solution than samples with a bacteriophilic surface do. The bacterial counts were determined and set in relation to each other. Using this assay, it could be proved that fewer bacteria stick to samples with ethacridine lactate compared to samples without ethacridine lactate. The transfer of the assay to other applications showed varying success. It could be proved that stents with benzalkonium chloride or cetylpyridinium chloride show a lower tendency for bacterial contamination than stents without any agent, too. It could not be finally proven that the sterilization procedure with ethylene oxide does not harm ethacridine lactate, but most probably, the agent is not affected. Also, it is not sure if the amounts of ethacridine lactate that are released six months after implantation, still are sufficient to reduce the bacterial colonization. The assay could only give a small hint that the amount is still sufficient. Comparing the immobilization methods by this assay, it could be clearly shown that the immobilization of the agent inside the polyurethane matrix by soaking is superior to the immobilization by spacers. The assay is not sufficiently sensitive to detect a difference between the samples with spacer-immobilized ethacridine lactate and the samples without antibacterial agent. If there are differences between the coatings made of amorphous carbon, they were not detected by the microbiological assay.