July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Tacrosolv: A novel aqueous tacrolimus eye drop formulation for the treatment of immune mediated eye diseases
Author Affiliations & Notes
  • Cornelia Siegl
    Marinomed Biotech AG, Austria
  • Marielle Koenig-Schuster
    Marinomed Biotech AG, Austria
  • Sabine Nakowitsch
    Marinomed Biotech AG, Austria
  • Christiane Koller
    Marinomed Biotech AG, Austria
  • Philipp Graf
    Marinomed Biotech AG, Austria
  • Wolfgang Sipos
    Clinical Department for Farm Animals and Herd Management, University of Veterinary Medicine Vienna, Austria
  • Eva Prieschl-Grassauer
    Marinomed Biotech AG, Austria
  • Footnotes
    Commercial Relationships   Cornelia Siegl, Marinomed Biotech AG (E), Marinomed Biotech AG (P); Marielle Koenig-Schuster, Marinomed Biotech AG (E); Sabine Nakowitsch, Marinomed Biotech AG (E), Marinomed Biotech AG (P); Christiane Koller, Marinomed Biotech AG (E), Marinomed Biotech AG (P); Philipp Graf, Marinomed Biotech AG (E); Wolfgang Sipos, None; Eva Prieschl-Grassauer, Marinomed Biotech AG (I), Marinomed Biotech AG (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6719. doi:
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      Cornelia Siegl, Marielle Koenig-Schuster, Sabine Nakowitsch, Christiane Koller, Philipp Graf, Wolfgang Sipos, Eva Prieschl-Grassauer; Tacrosolv: A novel aqueous tacrolimus eye drop formulation for the treatment of immune mediated eye diseases. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6719.

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

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Abstract

Purpose : Chronic inflammatory eye diseases, such as allergic conjunctivitis or dry eye are treated either with cyclosporine or tacrolimus as ophthalmic suspension. Marinomed aims to develop eye drops containing tacrolimus dissolved with the help of the Marinosolv technology, called Tacrosolv. Marinosolv allows the solubilization and thereby improvement of the bioavailability of practically insoluble drugs, such as tacrolimus, as dissolved drugs permeate faster into tissues. A set of experiments with formulations containing tacrolimus concentrations of up to 500 µg/ml dissolved in Marinosolv was conducted to investigate the permeation into cornea and conjunctiva of dissolved tacrolimus in comparison to the application of a tacrolimus suspension.

Methods : Porcine eyes were incubated ex-vivo for 60 minutes at room temperature after a single 50 µl topical application of 33, 66, 100, and 500 µg/ml Tacrosolv (corresponding to 1.7, 3.3, 5.0, 25.0 µg tacrolimus) compared to 1000 µg/ml Talymus (50 µg tacrolimus), a marketed eye drop suspension. Tissue concentrations in cornea and conjunctiva were evaluated by LC-MS/MS.

Results : The content of tacrolimus in the conjunctiva showed a linear relation to the applied concentration of Tacrosolv. After application of 33 µg/ml Tacrosolv, a tissue concentration of 205±87 ng/g conjunctiva tissue was found, which is at 10-fold higher than the effective serum concentration of 2-20 ng tacrolimus/ml in patients undergoing organ transplantation. After application of 500 µg/ml Tacrosolv, a tissue concentration of 4571±1347 ng/g conjunctiva was found, which is 2.6-fold higher than the concentration in eyes treated with Talymus. Tacrolimus content in the cornea showed a dose dependent increase and a peak concentration at 100 µg/ml of 1498 ng/g cornea, when treated with Tacrosolv. Application of 500 µg/ml Tacrosolv resulted in a tissue content of 791 ng/g in the cornea compared to 524±200 ng/g after a single application with Talymus.

Conclusions : The results demonstrated a concentration-dependent permeation of tacrolimus with the help of Marinosolv in both conjunctiva and cornea. A maximum concentration of 100 µg/ml in Tacrosolv should be sufficient to treat inflammatory anterior eye diseases, based on previous studies where a concentration of 2-20 ng/ml tacrolimus might be considered as the minimal effective concentration for controlling immune-mediated eye diseases.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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