September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Increased uptake of lipophilic immunosuppressive compounds in cornea and retina based on solubilization in an aqueous formulation.
Author Affiliations & Notes
  • Sabine Nakowitsch
    Marinomed Biotechnology, Vienna, Austria
  • Cornelia Kaintz
    Marinomed Biotechnology, Vienna, Austria
  • Philipp Graf
    Marinomed Biotechnology, Vienna, Austria
  • Marielle Koenig-Schuster
    Marinomed Biotechnology, Vienna, Austria
  • Eva Prieschl-Grassauer
    Marinomed Biotechnology, Vienna, Austria
  • Angelika Bodenteich
    Marinomed Biotechnology, Vienna, Austria
  • Andreas Grassauer
    Marinomed Biotechnology, Vienna, Austria
  • Footnotes
    Commercial Relationships   Sabine Nakowitsch, Marinomed Biotechnology (E); Cornelia Kaintz, Marinomed Biotechnlogy (E); Philipp Graf, Marinomed Biotechnology (E); Marielle Koenig-Schuster, Marinomed Biotechnology (E); Eva Prieschl-Grassauer, Marinomed Biotechnology (E); Angelika Bodenteich, Marinomed Biotechnology (E); Andreas Grassauer, Marinomed Biotechnology (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 275. doi:
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      Sabine Nakowitsch, Cornelia Kaintz, Philipp Graf, Marielle Koenig-Schuster, Eva Prieschl-Grassauer, Angelika Bodenteich, Andreas Grassauer; Increased uptake of lipophilic immunosuppressive compounds in cornea and retina based on solubilization in an aqueous formulation.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):275.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Second generation corticosteroids and many macrolide immunosuppressants show very poor solubility. Hence, these substances are formulated as dispersions for application to ocular tissues. However, dissolved drugs permeate faster into different ocular compartments and are less likely washed out before reaching therapeutic levels than solid disperse drug particles. Here, we show that the novel biocompatible aqueous formulation Marinosolv allows solubilizing of lipophilic drugs like Fluticasone propionate and Tacrolimus. For visualization of the increased uptake into cornea and retina of solubilized lipophilic compounds in comparison to dispersions, fluorescently labeled estradiol was used in porcine ex-vivo models.

Methods : Fluticasone propionate, Tacrolimus, and fluorescently labeled estradiol were solubilized in the Marinosolv formulation. The concentrations of dissolved compounds were determined by standard HPLC methods. For visualization of the permeation, fluorescently labeled estradiol was applied as Marinosolv solution or dispersion onto porcine eyes ex-vivo and the amount of compound was determined by light scattering microscopy (LSM).

Results : Fluticasone propionate, Tacrolimus and fluorescently labeled estradiol can be dissolved in Marinosolv, a formulation suitable for ocular application. An increase of solubility of approximately 200-fold was observed for all three compounds. The ex-vivo visualization experiment with fluorescently labeled estradiol clearly showed that dispersed estradiol hardly penetrates into eye compartments. In contrast, Marinolsov solubilized estradiol was detected within the cornea and the sclera/retina tissues in remarkable amounts.

Conclusions : Utilization of Marinosolv enables the solubilization of otherwise insoluble compounds for ocular application. The increased penetration of these compounds into ocular tissues, visualized with solubilized labeled estradiol, suggests an enhanced tissue availability of dissolved drugs in comparison to dispersions. The application of Marinosolv may enable the development of otherwise insoluble drugs for the treatment of ocular diseases.

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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