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B. Ruiz-Perez, T. Dowie, W. Schubert, P. Isom, P. Moslemy, M. Patane; A Non-Invasive Ocular Drug Delivery System That Delivers Substantially Greater Antibiotic Levels Than Topical Administration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5713.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate transscleral iontophoresis of antibiotics from various therapeutic classes including amikacin, tobramycin, ciprofloxacin, levofloxacin, ceftriaxone, erythromycin, clindamycin, and vancomycin (a tricyclic glycopeptide) in vitro and in vivo.
Initial in vitro testing was performed in Ussing chambers with rabbit sclera; constant current (+ or -) of 3 or 4 mA for 30 or 60 min was applied (no current for 30 or 60 min for topical passive controls). Transscleral in vitro delivery using an annular-shaped device was tested in Franz cells. The iontophoretic device was placed over hemisected rabbit eye mounted on the receptor chamber; constant current (+ or -) of 4 mA for 20 min was applied (no current for 20 min for topical passive controls). Samples collected from the receptor chambers of Ussing and Franz cells at various time points were analyzed for drug content by HPLC or LC/MS. The rate and extent of drug delivery achieved by iontophoresis was compared to topical passive delivery.In vivo iontophoretic delivery of vancomycin was tested in New Zealand white rabbits using an annular-shaped device; a single dose of vancomycin at + 4 mA for 10 min was administered (no current for 10 min for topical passive control). Animals were sacrificed immediately after dosing and vancomycin concentration in selected ocular tissues was analyzed by LC/MS.
Transscleral delivery of all antibiotics tested was substantially enhanced by iontophoresis compared to passive diffusion in Ussing chambers and Franz cells. Drug concentrations reached detectable levels in the receptor solution of Franz cells within 5 min of iontophoresis for all antibiotics tested. In vivo iontophoretic delivery of various formulations of vancomycin in rabbits resulted in several fold increases in aqueous humor and vitreous concentrations compared to topical passive controls.
Transscleral iontophoretic delivery of various antibiotics including low molecular weight compounds and vancomycin was demonstrated. Iontophoresis may offer a non-invasive method of delivery to achieve therapeutic levels of antibiotics in anterior and posterior ocular tissues.
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