April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
DNA-based nanoparticles as potential drug carriers for the treatment of anterior segment diseases
Author Affiliations & Notes
  • Sven Schnichels
    University Eye Hosp Tuebingen, Centre for Ophthalmology Tuebingen, Tuebingen, Germany
  • Jan Willem de Vries
    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
  • Lisa Strudel
    University Eye Hosp Tuebingen, Centre for Ophthalmology Tuebingen, Tuebingen, Germany
  • Minseok Kwak
    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
  • Johanna Hofmann
    University Eye Hosp Tuebingen, Centre for Ophthalmology Tuebingen, Tuebingen, Germany
  • Karl U Bartz-Schmidt
    University Eye Hosp Tuebingen, Centre for Ophthalmology Tuebingen, Tuebingen, Germany
  • Martin Stephan Spitzer
    University Eye Hosp Tuebingen, Centre for Ophthalmology Tuebingen, Tuebingen, Germany
  • Andreas Hermann
    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
  • Footnotes
    Commercial Relationships Sven Schnichels, University Eye Hospitlal Tübingen (P); Jan Willem de Vries, University Groningen (P); Lisa Strudel, None; Minseok Kwak, None; Johanna Hofmann, None; Karl Bartz-Schmidt, None; Martin Spitzer, University eye hospital Tübingen (P); Andreas Hermann, University Groningen (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 468. doi:
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      Sven Schnichels, Jan Willem de Vries, Lisa Strudel, Minseok Kwak, Johanna Hofmann, Karl U Bartz-Schmidt, Martin Stephan Spitzer, Andreas Hermann; DNA-based nanoparticles as potential drug carriers for the treatment of anterior segment diseases. Invest. Ophthalmol. Vis. Sci. 2014;55(13):468.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Currently anterior segment diseases can only be treated with multiple daily doses of highly concentrated drugs. Treatment is severely hindered because only approximately 1 5% of the applied drug stays on the eye long enough to be effective. The major part is washed away by eye lid movement and tear fluid. Due to the high concentration of the drug often systemic and local side effects are caused. Additionally, the repeated application of eye drops and the fact that they often cause blurred vision generally cause a reduced compliance. By increasing the duration time of the medication a lower regime and a lower drug concentration can be attained.

Methods: We have developed a drug carrier for eye drops based on DNA nanoparticles (NPs) that have high affinity to the cornea. This NP can be loaded with many kinds of drugs through three different binding possibilities, two of them leaving the drug unchanged. To evaluate the NP, they were conjugated to a fluorescent marker and dropped on pig (from the slaughterhouse) and rat eyes (conscious animals). Afterwards the eyes were processed for histology. To exclude toxicity of the NPs, three ocular cell lines were incubated with the NP for 24h and cell viability, cell amount and caspase 3/7 activity was measured. Additionally our NP was conjugated to gold-particles and analyzed with electron microscopy to detect the exact location of the NP.

Results: In this proof-of-concept study in pig and rat eyes the NP showed excellent binding to the cornea epithelium compared to the pristine drug molecules. The NPs were even found up to 4h after application to conscious rats. Our NP did not show any toxicity at the used concentration for our applied NP eye drops in any ocular cell line tested. EM-pictures proof that the NPs are attached to the surface of the cornea.

Conclusions: Thus, using this novel carrier system we are able to significantly increase the adherence time of the drug in the eye. As a consequence, a lower frequency of eye drop administration is feasible which is beneficial for the compliance and treatment of the patient. Additionally, a lower drug concentration can be used, what drastically reduces systemic and local side effects. Another favorable feature of the delivery system is that drugs currently not in use due to their severe side effects could become utilized. A first application with drugs is shown on another abstract from our group.

Keywords: 607 nanotechnology  
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