The antimicrobial activity of two cyanobacterial exometabolites, norharmane (9H-pyrido(3,4-b)indole) and 4,4'-dihydroxybiphenyl, was determined in suspension assays. Good anticyanobacterial activities (concentrations of 8-80 microg ml(-1)) and moderate antibacterial (16-160 microg ml(-1)) and antifungal (32-40 microg ml(-1)) activities were found for both compounds. The natural function as allelopathic chemicals and a possible applicability as antifouling agents or leads for the development of new antifouling chemicals are discussed.
In clinical applications, colonization of metal implants by adhesive and biofilm-forming bacteria not only prolong healing but create additional healthcare costs for implant revision and antimicrobial treatment. An in vitro assay was established investigating the antimicrobial surface activity of external fixation pins intended for use in bone fractures and deformities. Test articles made out of stainless steel and coated with a polymer-containing nanoparticulate silver were compared to non-coated reference controls out of stainless steel, copper and titanium. Staphylococcus epidermidis, known as a predominant cause for implant-related infections was used as test organism. Test pins and bacteria were incubated for a period of 20 h found to be sufficient for initiating biofilm formation. After removing non- and low-adherent bacteria by rinsing, two methods were used to isolate high-adherent (sessile) bacteria from the implant surfaces. Besides shaking the implants in a solution containing small glass beads, a cytobrush technique was used to mechanically harvest viable bacteria. Finally, the amount of detached bacteria was determined by plate counts. Several parameters identified to be critical within the different removal procedures such as the inoculum concentration and the shaking time in the presence of glass beads as well as time of the cytobrush treatment were analysed. The final test scheme resulted in the use of an inoculum of 10(5) colony forming units (CFU) per millilitre, ten rinsing steps for the removal of low adherent bacteria and 5 min of shaking in the presence of glass beads, detaching the high-adherent bacteria. Due to subjective variations impacting the outcome of the procedure, the cytobrush technique was not favoured and finally rejected. Using the in vitro assay developed, it could be demonstrated that fixation pins coated with silver show a 3 log step reduction in the number of biofilm-forming bacteria compared to a non-coated stainless steel or titanium implant. Pins made out of copper showed the highest antimicrobial efficacy, as the number of detached bacteria was found to be below the detection limit, they served as a positive control within this test.
Nanostructuring of drug delivery systems offers many promising applications like precise control of dissolution and release kinetics, enhanced activities, flexibility in terms of surface coatings, integration into implants, designing the appropriate scaffolds or even integrating into microelectronic chips etc. for different desired applications. In general such kind of structuring is difficult due to unintentional mixing of chemical solvents used during drug formulations. We demonstrate here the successful solvent-free fabrication of micro-nanostructured pharmaceutical molecules by simple thermal evaporation (TE). The evaporation of drug molecules and their emission to a specific surface under vacuum led to controlled assembling of the molecules from vapour phase to solid phase. The most important aspects of thermal evaporation technique are: solvent-free, precise control of size, possibility of fabricating multilayer/hybrid, and free choice of substrates. This could be shown for twenty eight pharmaceutical substances of different chemical structures which were evaporated on surfaces of titanium and glass discs. Structural investigations of different TE fabricated drugs were performed by atomic force microscopy, scanning electron microscopy and Raman spectroscopy which revealed that these drug substances preserve their structurality after evaporation. Titanium discs coated with antimicrobial substances by thermal evaporation were subjected to tests for antibacterial or antifungal activities, respectively. A significant increase in their antimicrobial activity was observed in zones of inhibition tests compared to controls of the diluted substances on the discs made of paper for filtration. With thermal evaporation, we have successfully synthesized solvent-free nanostructured drug delivery systems in form of multilayer structures and in hybrid drug complexes respectively. Analyses of these substances consolidated that thermal evaporation opens up the possibility to convert dissoluble drug substances into the active forms by their transfer onto a specific surface without the need of their prior dissolution.
These first investigations of preserved contact lenses indicate a new possibility for reducing lens-induced infections of the eyes. Due to the weak efficacy against the gram-positive species S. aureus a silver layer probably cannot replace other sterilization procedures completely, but it may represent an additional protection from contamination. Side effects to the eyes due to the negligible toxicity of oligodynamics silver concentrations, such are known to occur with high silver concentrations, should be not expected, but possible allergic reactions caused by the silver-ions should be investigated.
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