Pharmacokinetic and Toxicity Investigations of a New Intraocular Lens with a Dexamethasone Drug Delivery System: A Pilot Study

Abstract

Aim: To investigate the short-term safety and pharmacokinetic behavior of a new intraocular lens containing a dexamethasone drug delivery system (IOL-DDS) in rabbit eyes. Methods: A modified polymethylmethacrylate IOL containing a biodegradable dexamethasone DDS was implanted into the posterior chamber of the right eyes of 9 New Zealand white rabbits. Serial slitlamp and indirect ophthalmoscopic examinations (including grading of intraocular inflammation) were performed. After 3, 6 and 9 days, the rabbits were euthanized and the globes were removed for histological examination and for determination of dexamethasone levels in the aqueous humor and in the vitreous. Analysis of dexamethasone concentrations was performed by ELISA. Results: Therapeutic concentrations of dexamethasone were detectable in the aqueous and vitreous of the study eyes throughout the 9-day period in all tested animals. The mean aqueous dexamethasone concentration (ng/ml, ±SD) was 1,015.42 (±43.05), 970.11 (±32.47) and 757.58 (±30.19) and the mean vitreous concentration (ng/ml, ±SD) was 399.82 (±38.05), 287.38 (±34.47) and 268.15 (±32.00) at 3, 6 and 9 days after the surgical procedure, respectively. No corneal or retinal histological changes were observed during the study period. Conclusion: The IOL-DDS is effective in delivering therapeutic concentrations of dexamethasone to the aqueous and vitreous, without acute damage to the cornea and retina. Further controlled studies in the same animal model are under way to determine the potential value of this lens in the prevention and treatment of inflammation following cataract surgery.

Pharmacokinetic Study of Dexamethasone Disodium Phosphate using Intravitreal, Subconjunctival, and Intravenous Delivery Routes in Rabbits

“…The high potency and relatively acceptable toxicity of this compound, combined with its multifunctional roles as an anti-inflammatory, antiangiogenic, and antipermeability agent, confirm that it is a candidate for various ocular drug-delivery platforms. [13][14][15] The pharmacokinetics and local distribution of this compound in the eye have been investigated in the past 15,16 ; however, we did not find information regarding the comparison between the pharmacokinetics of IV, SC, and IVT delivery. Figure 1A and 1B indicates a very rapid conversion of the prodrug to the drug.…”

Drug-Induced Secondary Cataract Prevention: Experimental ex vivo and in vivo Results with Disulfiram, Methotrexate and Actinomycin D

“…and monkeys [47,48] . Furthermore, different methods for drug application were tested [26,33,34,36,47,49] . Irrespective of the drug application, the effective local drug concentration must have been adequate to reduce the LEC viability to result in a long-term decrease in PCO.…”

“…In addition, adhesion inhibitors [32] and osmotic effective solutions [24] were tested. In several studies, different drug delivery systems [33][34][35][36] were investigated in order to provide a longer and more effective impact on LECs. To avoid toxic side effects, an irrigation device may allow for the isolated safe delivery of pharmacological agents into the sealed capsule following cataract surgery [24,37,38] .…”

Drug-Eluting Intraocular Lenses

“…Combination of an IOL with one or more drug-loaded inserts in a joining device (Figure 1) is perhaps the most direct approach to achieve intraocular release in the environment surrounding the IOL [26,27]. The current knowledge about design and synthesis of biodegradable inserts leads to suitable intraocular drug depots that efficiently regulate the release rate [28,29].…”