May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
In vitro Passive and Iontophoretic Permeation of Insulin Through Human Sclera
Author Affiliations & Notes
  • G. Ferrari
    University of Parma, Parma, Italy
    Institute of Ophthalmology,
  • S. Nicoli
    University of Parma, Parma, Italy
    Department of Pharmacy,
  • M. Quarta
    University of Parma, Parma, Italy
    Department of Pharmacy,
  • P. Govoni
    University of Parma, Parma, Italy
    Department of Histology and Embrology,
  • C. Macaluso
    University of Parma, Parma, Italy
    Institute of Ophthalmology,
  • P. Santi
    University of Parma, Parma, Italy
    Department of Pharmacy,
  • Footnotes
    Commercial Relationships  G. Ferrari, None; S. Nicoli, None; M. Quarta, None; P. Govoni, None; C. Macaluso, None; P. Santi, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1812. doi:https://doi.org/
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      G. Ferrari, S. Nicoli, M. Quarta, P. Govoni, C. Macaluso, P. Santi; In vitro Passive and Iontophoretic Permeation of Insulin Through Human Sclera. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1812. doi: https://doi.org/.

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

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Abstract

Purpose: : It has been proposed that the maintenance of low concentration of insulin in the retina could improve diabetic retinopathy; transscleral iontophoresis can represent a minimally invasive technique to deliver high molecular weight drugs to the posterior segment of the eye. The purpose of this work was to evaluate feasibility of transscleral iontophoresis of insulin. An additional objective was to check the effect of current on tissue integrity.

Methods: : Isolated human sclera was mounted on vertical diffusion cells. The donor compartment contained insulin solution 1 mg/ml at pH 7.4 or 3.5. In the current assisted experiments, anodal and cathodal iontophoresis was applied for 20 min (current intensity: 1.75 or 3.5 mA).Histology was performed on the sclera before and after iontophoresis using hematoxylin-eosin and Sirius red (a selective histochemical collagen stain) to search for any tissue damage.

Results: : When insulin solution (1 mg/ml) was applied to human sclera at pH 7.4 the transscleral flux obtained was 9.1±2.2 µg cm-2h-1 . The permeability profile was characterized by a lag time of about 1 hour.When iontophoresis was applied for 20 minutes, the obtained fluxes and lag time were not significantly different from passive permeation. Transscleral passive fluxes obtained at pH 3.5 and pH 7.4 were comparable.Preliminary results obtained applying anodal iontophoresis at pH 3.5 showed a higher permeation and absence of lag time, suggesting the potential usefulness of this technique.Histologic sections showed normal architecture and well organized collagen fibres; no difference could be detected between pre and post treatment specimens.

Conclusions: : Insulin has been delivered to the eye by topical (eye drops), peribulbar, and intravitreal routes; however, to our best knowledge, it is the first time transscleral iontophoresis was attempted. Human sclera is permeable to insulin, although a relatively long lag time was observed in passive diffusion conditions. When the current was applied the lag time was reduced and the flux increased, suggesting that transscleral iontophoresis could be a useful tool for improving insulin delivery to the posterior segment of the eye.

Keywords: sclera • diabetic retinopathy • drug toxicity/drug effects 
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