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Enhanced Transscleral Iontophoretic Transport with Ion-Exchange Membrane

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Purpose

Transscleral iontophoresis has been recently re-examined for drug delivery to the back of the eye. In conventional iontophoresis, due to the relatively high electromobility of the endogenous competing ions (counterions) relative to that of the drug ion in the tissue barrier, the efficiency of iontophoretic drug delivery is generally low. The objective of the present study was to examine ion-exchange membrane-enhanced transscleral iontophoretic transport in which the ion-exchange membrane in series with the sclera can hinder the transport of the competing counterions and selectively allow the transport of the permeant across the sclera.

Methods

The physical properties of the Ionac ion-exchange membrane and excised rabbit sclera were determined in equilibrium uptake experiments and in passive and iontophoretic transport experiments with salicylate, tetraethylammonium, urea, and mannitol. Transscleral experiments with the ion-exchange membrane were conducted with salicylate and excised rabbit sclera in vitro. The contribution of electroosmosis to electrotransport during transscleral iontophoresis was assessed with urea and mannitol.

Results

The ion-exchange membrane is highly positively charged and has a small effective pore size. The sclera is relatively porous with a large effective pore size and low pore tortuosity. The sclera is also net negatively charged but this does not significantly affect the transport of small ions. A three-fold steady-state transscleral flux enhancement of salicylate was observed in ion-exchange membrane-enhanced iontophoresis over conventional transscleral iontophoresis without the membrane. Such enhancement was relatively independent of the applied electric current density and the thickness of the studied ion-exchange membrane assembly. Although the ion-exchange membrane altered transscleral electroosmosis, the contribution of electroosmosis to electrotransport was not significant.

Conclusions

The present study has demonstrated the potential of ion-exchange membranes for enhancing iontophoretic transport and drug delivery.

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Acknowledgments

This research was supported in part by NIH Grant EY015181. The authors thank Dr. Rajan P. Kochambilli for his help in the preparation of the experiments, Matthew S. Hastings and Dr. David J. Miller at Aciont Inc. (Salt Lake City, UT), Dr. Yanhui Zhang and Dr. Henry S. White for helpful discussion, Dr. Aniko Szabo and Dr. Lisa M. Pappas for their help in statistical analyses.

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Author notes

  1. S. Kevin Li

    Present address: College of Pharmacy, University of Cincinnati, 3225 Eden Avenue, Rm 136 HPB, Cincinnati, Ohio, 45267, USA

Authors and Affiliations

  1. Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112, USA

    S. Kevin Li, Honggang Zhu & William I. Higuchi

  2. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, 45267, USA

    S. Kevin Li

Authors
  1. S. Kevin Li
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  2. Honggang Zhu
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  3. William I. Higuchi
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Correspondence to S. Kevin Li.

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Li, S.K., Zhu, H. & Higuchi, W.I. Enhanced Transscleral Iontophoretic Transport with Ion-Exchange Membrane. Pharm Res 23, 1857–1867 (2006). https://doi.org/10.1007/s11095-006-9010-9

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  • DOI: https://doi.org/10.1007/s11095-006-9010-9

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