June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Travoprost loaded lipid DNA-nanoparticles as a new and improved treatment for glaucoma
Author Affiliations & Notes
  • Sven Schnichels
    University Eye Hosp Tübingen, Centre for Ophthalmology Tübingen, Tuebingen, Germany
  • Jan Willem de Vries
    University Eye Hosp Tübingen, Centre for Ophthalmology Tübingen, Tuebingen, Germany
  • Agnieszka Gruszka
    University Eye Hosp Tübingen, Centre for Ophthalmology Tübingen, Tuebingen, Germany
  • Karl Ulrich Bartz-Schmidt
    University Eye Hosp Tübingen, Centre for Ophthalmology Tübingen, Tuebingen, Germany
  • Sascha Dammeier
    Institute for Ophthalmic Research, Tübingen, Germany
  • Andreas Herrmann
    University Groningen, Groningen, Netherlands
  • Martin Stephan Spitzer
    University Eye Hospital, Hamburg, Germany
  • Jose Hurst
    University Eye Hosp Tübingen, Centre for Ophthalmology Tübingen, Tuebingen, Germany
  • Footnotes
    Commercial Relationships   Sven Schnichels, University Eye Hospital Tübingen (P); Jan Willem de Vries, University Groningen (P); Agnieszka Gruszka, None; Karl Bartz-Schmidt, None; Sascha Dammeier, None; Andreas Herrmann, University Groningen (P); Martin Spitzer, University Eye Hospital Tübingen (P); Jose Hurst, None
  • Footnotes
    Support  EXIST Forschungstransfer from the German Federal Ministry for Economic Affairs and Energy
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4105. doi:
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      Sven Schnichels, Jan Willem de Vries, Agnieszka Gruszka, Karl Ulrich Bartz-Schmidt, Sascha Dammeier, Andreas Herrmann, Martin Stephan Spitzer, Jose Hurst; Travoprost loaded lipid DNA-nanoparticles as a new and improved treatment for glaucoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4105.

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

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Abstract

Purpose : Our drug delivery platform based on lipid-modified DNA nanoparticles (NPs) was already presented in previous years showing improved topical delivery of antibiotics, biosafety of the carrier and first successful delivery to the retina upon intravitreal injection. Lipid DNA-NPs have an intrinsic affinity to the ocular surface and can be used as broadly functionalizable carriers for enhanced drug delivery. Here the anti-glaucoma drug travoprost was loaded into the NP (Trav-NPs) via aptameric interactions, leaving the chemical structure of the drug unmodified. The effects of the Trav-NPs were compared in-vitro, ex-vivo and in-vivo to the commercial drug formulation.

Methods : Fluorescently labeled Trav-NPs eye drops were applied onto ex-vivo pig eyes from an abattoir and in-vivo on rats. After different incubation times, the adhesion to the corneas was assessed via fluorescent microscopy and fluorophotometry. To evaluate the safety profile of the NPs, primary corneal epithelial cells were treated with Trav-NPs and cell viability was measured. Furthermore, the NPs were dropped on eyes using different dosing regimens. Cornea sections were then screened for apoptosis. The efficiency of delivery to ex-vivo and-in vivo tissue was determined with liquid chromatography–mass spectrometry (LC-MS) and compared to the commercially available formulation. Finally, the Trav-NPs and Travatan were dropped on rodents to evaluate the IOP lowering effect.

Results : Trav-NPs showed a long-lasting adherence to ex-vivo pig and in-vivo rat corneas and were present on the in-vivo cornea even after 60 minutes from eye drop installation. Both in-vitro and in-vivo toxicity experiments proved the biosafety of the Trav-NP. Quantification via LC-MS revealed that Trav-NPs deliver at least double amount of the drug at every time-point investigated compared to Travatan. Finally efficacy of the Trav-NPs was proven by the IOP lowering effect in-vivo in rats and glaucoma-affected mice.

Conclusions : Our data proves the functionality of our DNA-based NP carrier system as anti-glaucoma drug delivery vehicle. We confirmed that the drug formulated with DNA NPs remained functional, that they are non-toxic and the eye-adhering NPs delivered higher amount of the drug to the site of action. These findings allow further investigation with our NP carrier system to improve the treatment for glaucoma patients by delivering drugs more efficiently to the eye.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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