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Martin Stephan Spitzer, Sven Schnichels, Lisa Strudel, Johanna Hofmann, Karl U Bartz-Schmidt, Andreas Hermann, Jan Willem de Vries; Enhanced antibiotic delivery through DNA-based nanoparticles. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2162.
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Currently diseases of the anterior eye segment, like corneal infections, can only be treated with multiple daily doses of highly concentrated drugs. Therefore it is desired to explore a delivery system, which binds to the surface tissue and thus prolongs the effective half-life of the antibiotic and enhances uptake into the eyes. One promising new concept is the use of DNA nanoparticles.
In this study two antibiotics (kanamycin B & neomycin B) were conjugated to DNA-based nanoparticles (NPs). The details of the particles are presented on another poster of our group. After successful proof-of-concept experiments they were tested on living rats. The uptake of the antibiotic-NPs was tested on human corneal tissue. Additionally, the functionality of the antibiotics was evaluated in-vitro in a minimum inhibitory concentration test (MIC-Test) using E.coli. To mimic conditions on the ocular surface, nucleases (NAs) were added to the cell suspension with antibiotic functionalized NPs. The NAs digest the NP and as a consequence the antibiotic is released. Afterwards, corneas of eyes treated with our nanoparticle antibiotic conjugate were transferred to agar plates infected with E. coli to prove functionality on the cornea.
Good binding of tested antibiotic-DNA-nanoparticles onto the cornea epithelium was observed. Antibiotics are available in the corneal epithelium of the rat eye for a period of at least 30 min, which is longer than the antibiotic alone. On the human cornea the antibiotics with the NP were found for 2h longer than without the NP. For neomycin B the antibiotic is found not to be active when it is complexed to the NP. However, upon addition of NAs, activity is restored. For kanamycin the difference is less pronounced, as the antibiotic is still pharmaceutically active when bound to the NP. Nevertheless, the addition of NAs yields a higher activity of the antibiotic at lower concentrations
We present a DNA-nanoparticle carrier system with a successful delivery of an ophthalmic drug. A prolonged availability of the antibiotic on the eye will increase the uptake. Functionality of the drug depends on the binding constant of the drug to the NP and is restored in the presence of nucleases; all drugs tested were still pharmaceutically active. This study shows that our DNA-NP-based system works and further research should be performed in animal studies to explore the potential of this carrier system.
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