Purchase this article with an account.
J. W. Higuchi, W. I. Higuchi, K. Papangkorn, S. K. Li, R. P. Kochambilli, A. L. Tuitupou, D. C. Mix, Jr.; A Sustained Release System of Dexamethasone Sodium Phosphate With Calcium Ion Delivered From a Visulex® Passive Lens Device. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5996.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
A previous study has shown that a sustained release depot of triamcinolone acetonide phosphate (TAP) in the eye is achievable with transscleral iontophoresis of TAP and calcium ion (Ca). This TAP-Ca depot was found to be efficacious in an experimentally endotoxin induced uveitis (EIU) rabbit model. More recent data have suggested that such depots may form via passive diffusion, i.e., without the use of iontophoresis. The objective of this study was 1) to test the hypothesis that a sustained release depot can form in the eye after transscleral passive delivery of dexamethasone sodium phosphate (DSP) and Ca, and 2) to evaluate the efficacy of this depot in the EIU rabbit model.
All experiments were performed with New Zealand white rabbits using a transscleral passive delivery lens device (P-12), which contained 0.5M DSP and/or 1M CaCl2. P-12 was applied to the rabbit eye surface with treatment durations of 15 to 30 min. For the pharmacokinetic (PK) study, rabbits were sacrificed at predetermined time points (0-24 h) after treatment, and the total amounts of the drug in the treated eyes were determined in terms of DSP equivalent by HPLC. For the efficacy study, EIU was induced by an intravitreal injection of lipopolysaccharide from E. Coli. The efficacy of the depot in treating EIU was evaluated for 4 days and compared with no treatment.
The amounts of DSP delivered into the eye were similar for the passive delivery of DSP (507µg) and DSP-Ca (410µg). However, the amounts of the drug remaining in the eye were significantly different between these 2 groups at 4 h (15µg for DSP alone vs. 175µg for DSP-Ca). The half-life of total DSP in the eye was around three times longer with DSP-Ca than with the DSP alone. In the efficacy study, the uveitis score (on the scale of 0 to 4) for no treatment was 3.5 ± 0.8 whereas those for DSP-Ca were 1.2 ± 0.7 for 15 min treatment and 1.3 ± 0.9 for 30 min treatment.
A sustained release DSP-Ca depot can form in the eye after transscleral passive delivery of DSP and Ca. The combination of transscleral passive delivery of DSP and Ca was found to be effective in the EIU rabbit model.
This PDF is available to Subscribers Only