April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Effect Of Formulation Factors On The Trans-scleral Iontophoretic Transport Of A 40kDa Dextran In-vitro
Author Affiliations & Notes
  • Sara Nicoli
    Department of Pharmacy, University of Parma, Parma, Italy
  • Silvia Pescina
    Department of Pharmacy, University of Parma, Parma, Italy
  • Patrizia Santi
    Department of Pharmacy, University of Parma, Parma, Italy
  • Footnotes
    Commercial Relationships  Sara Nicoli, None; Silvia Pescina, None; Patrizia Santi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3248. doi:
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      Sara Nicoli, Silvia Pescina, Patrizia Santi; Effect Of Formulation Factors On The Trans-scleral Iontophoretic Transport Of A 40kDa Dextran In-vitro. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3248.

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

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Purpose: : The aim of the work was to study in vitro, across isolated porcine sclera and across the trilayer sclera-choroid-Bruch’s membrane (SCB), the effect of iontophoresis on the permeation of a 40KDa dextran (FD-40), chosen as model compound of high molecular weight neutral drugs. In particular, the effect of vehicle composition (in term of buffer type and ionic strength) and current intensity were investigated. Additionally the post-iontophoretic transport of FD-40 through SCB was studied.

Methods: : Permeation experiments were performed in Franz-type diffusion cells using either porcine sclera or the trilayer SCB as barrier. The donor compartment contained FD-40 500 µg ml-1 dissolved in HEPES, PBS or PB. In the iontophoretic experiments, the current (intensity: 0.3 - 1 - 1.75 - 3 - 4.2 mA; anodal) was applied for 2 hours by a constant current generator. Experiments were also performed to evaluate the possible damaging effect (recorded as an increase of permeability) of current application on the trilayer. Additional experiments were performed to evaluate the possible role of the sclera as a drug reservoir.

Results: : Ionic strength was the more relevant parameter influencing the iontophoretic transport of FD-40, while the type of buffer (phosphate vs HEPES) was not relevant. The enhancement obtained increases - although in a stepwise way - with current intensity, after a threshold value of approximately 1.5 mA (2.5 mAcm-2). The inclusion of choroid and Bruch’s membrane, reduces, as expected, the permeation of FD-40, but iontophoresis is able to significantly promote FD-40 transport also through this more complex barrier, without altering its permeability. Finally, the study of the post-iontophoretic transport highlights the formation of a pronounced FD-40 reservoir inside the sclera.

Conclusions: : The results confirm the importance of formulation parameters during transscleral iontophoresis of a neutral high molecular weight hydrophylic compound transported by elctroosmosis.

Keywords: sclera 

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