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Lisa Strudel, Jose Hurst, Jan Willem de Vries, Agnieszka Gruszka, Karl Ulrich Bartz-Schmidt, Andreas Herrmann, Martin Stephan Spitzer, Sven Schnichels; Lipid DNA Nanoparticles – a versatile vehicle for anterior segment drug delivery. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5684. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The efficacy of eye drops is impaired by the short survival time of the drug on the eye surface. As a consequence, topical administration of ocular therapeutics requires high drug doses and frequent administration, still rarely providing high bioavailability. One opportunity in the treatment of ophthalmic diseases lies in nanotechnology.
Nucleic acids represent very appealing building blocks for the construction of nanoparticles (NPs) with great application potential in the field of drug delivery. Introducing hydrophobic chains at the nucleobase thymine enabled the synthesis of amphiphilic DNA strands (12mers with 4 lipid modified thymines at the 5’ end), which self-assemble into micelles. In a single step they can be equipped with different drugs by hybridization with an aptamer not requiring any chemical modification of the active pharmaceutical ingredient (API). Four drugs –two antibiotics and two glaucoma drugs- were bound via aptameric interactions to the carrier system: Neomycin, Kanamycin, Travoprost and Brimonidine.
The effects of the fluorescently labeled DNA-NPs were compared ex-vivo and in-vivo to formulations with the pristine drugs. After different incubation times, the adhesion to the corneas was assessed via fluorescence microscopy and fluorophotometry. Our DNA-NPs adhered to the corneal surface for extended periods of time. The efficiency of Travoprost delivery was measured with liquid chromatography–mass spectrometry (LC-MS) and compared to the commercially available formulation. Quantification revealed that our NPs enable delivery of at least double the amount of the drug at every time-point investigated and most importantly four times more Travoprost at the four hour time-point. To assess the efficacy and functionality of the APIs, murine eyes were infected with Pseudomonas. Antibiotics delivered with our NP showed a much faster and more efficient bactericidal effect. With our NP-system the same efficacy can be reached with a 25x lower concentration on infected animals. Finally, the NPs were confirmed to be applicable even for human tissue.
Our data successfully prove the applicability of a DNA-based drug delivery system for the treatment of a major eye disease, i.e. glaucoma or corneal infections. These results will fuel further research into easy-to-prepare and modular drug delivery platforms tackling also other indications of the anterior of the eye.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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