September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
In-vitro and in-vivo toxicological evaluation of alkyl-modified DNA nanoparticles
Author Affiliations & Notes
  • Katharina Froessl
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Jan Willem De Vries
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Johanna Wude
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Jose Hurst
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Agnieszka Gruszka
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Karl-Ulrich Bartz-Schmidt
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Andreas Hermann
    Universität Groningen, Groningen, Netherlands
  • Martin Stephan Spitzer
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Sven Schnichels
    Universitätsaugenklinik Tübingen, Tübingen, Germany
  • Footnotes
    Commercial Relationships   Katharina Froessl, None; Jan Willem De Vries, University Groningen (P); Johanna Wude, None; Jose Hurst, None; Agnieszka Gruszka, None; Karl-Ulrich Bartz-Schmidt, None; Andreas Hermann, University Groningen (P); Martin Spitzer, Alcon (R), Novartis (F), Universität Tübingen (P); Sven Schnichels, Novartis (F), Universität Tübingen (P)
  • Footnotes
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Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5054. doi:
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      Katharina Froessl, Jan Willem De Vries, Johanna Wude, Jose Hurst, Agnieszka Gruszka, Karl-Ulrich Bartz-Schmidt, Andreas Hermann, Martin Stephan Spitzer, Sven Schnichels; In-vitro and in-vivo toxicological evaluation of alkyl-modified DNA nanoparticles. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5054.

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

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Abstract

Purpose : Last year we presented several novel DNA-based nanoparticles (NPs) to overcome current shortcomings in the treatment of anterior eye segment diseases. This year we will present another important issue in the development of a new drug delivery platform: safety and toxicity. Furthermore, we also quantified the amount of NP present on the cornea after dropping them to the eye.

Methods : To exclude toxicity of the NPs, primary corneal epithelial cells were incubated with a variety of NPs for 24 h and cell viability via MTS-assay, cell amount via crystal violet staining and apoptosis via caspase 3/7 assay was measured. Additionally, the same tests were performed using two different ocular cell lines. In order to further determine the toxicity profile, the NPs were dropped on rat eyes at different time-points and dosing regimens. Sections of the eyes were then analyzed via TUNEL-assay for apoptosis. As a last toxicity evaluation the upregulation of inflammatory pathways was screened. Through a PCR assay the influence of the NPs on expression of toll-like receptors (TLR), interleukins (IL) and tumor necrosis factor alpha (TNF-α) was determined. Finally, the residence time of the NPs was evaluated using an ocular fluorophotometer

Results : Neither in-vitro cell toxicity screening nor the in-vivo experiments showed any toxicity. Even more, higher concentrations than the effective dose or an increased dropping interval could not cause a negative effect. Also the evaluation of TLR, IL and TNF-α regulation showed normal expression levels. Additionally, evaluation of the residence time by ocular fluorophotometry showed that the NP gets washed out slowly and is detectable for up to 2 hours after application, whereas a small molecule control is already removed after 5 minutes.

Conclusions : Thorough and extensive in-vivo and in-vitro testing confirmed the local safety of our NP-carriers system. The previously shown better efficacy could now be confirmed with quantitative numbers. These important findings allow the further safe utilization of the NP platform for ocular drug delivery. Nevertheless, further studies on systemic toxicity and bio-distribution need to be performed before clinical trials can be performed.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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