September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Long-term latanoprost release from a subconjunctival drug delivery system
Author Affiliations & Notes
  • Franziska Kopp
    Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany
  • Thomas Eickner
    Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany
  • Karen Falke
    Department of Ophthalmology, University Medical Center Rostock, Rostock, Germany
  • Rudolf Guthoff
    Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany
    Department of Ophthalmology, University Medical Center Rostock, Rostock, Germany
  • Footnotes
    Commercial Relationships   Franziska Kopp, None; Thomas Eickner, None; Karen Falke, None; Rudolf Guthoff, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3019. doi:
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      Franziska Kopp, Thomas Eickner, Karen Falke, Rudolf Guthoff; Long-term latanoprost release from a subconjunctival drug delivery system. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3019.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : The efficiency of topical glaucoma treatment is impaired by poor patient compliance. Local drug delivery systems providing sustained release of active agents are a promising new therapeutic approach. In this experimental study a subconjunctival, latanoprost (LP)-loaded, in situ polymerizing delivery system for treatment of primary open angle glaucoma was investigated.

Methods : Five female New Zealand White rabbits received subconjunctival injection of a latanoprost-loaded polymer depot in the right eye (93.0 ± 12.0 µg LP). The polymer is a two-component system consisting of hyaluronic acid and an ethylene glycol dilactic acid derivate (ELA-NCO). To assess drug release, aqueous humor (AH) and tear fluid of the treated and the contralateral eye, as well as arterial blood were collected every three weeks. Concentrations of latanoprost and latanoprost acid (LA) were determined in all samples with LCMS. The intraocular pressure (IOP) was monitored for 6 weeks prior to and for 5 months after injection. Measurements were performed once a week with the Icare TAO1 tonometer.

Results : Latanoprost was detected in aqueous humor of the treated and the contralateral eye 30 minutes after injection, 0.55 ± 0.24 ng/ml and 1.33 ± 0.82 ng/ml, respectively. Serum levels of LP after 30 minutes were 1.92 ± 2.00 ng/ml. Similar concentrations were found after 24 hours in AH of both eyes (treated: 0.75 ± 0.44 ng/ml; untreated: 1.17 ± 0.75 ng/ml) and in serum (1.69 ± 1.43 ng/ml). After 6 weeks LP concentrations in AH were below the quantification limit of 0.1 ng/ml, but still detectable in serum after 9 weeks (0.59 ± 0.93 ng/ml). The active compound latanoprost acid was detected after 24 hours in aqueous humor of the treated eye (2.94 ± 1.10 ng/ml), but not thereafter. LP and LA were also detected in tear fluid. IOP did not change significantly after depot application.

Conclusions : Detection of the biologically active compound latanoprost acid in aqueous humor proves that subconjunctival injection is a suitable delivery route for the ester prodrug. The data show that an in situ polymerizing, two-component drug delivery system provides long-term latanoprost release in the ng/ml range. This study serves as proof-of-concept. Future investigations will be conducted to adjust drug release kinetics to therapeutic requirements.

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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