Sustained-release device nondegradable

IMPLANTED NONDEGRADABLE SUSTAINED-RELEASE DEVICES Description of Drug Delivery System... 

A rabbit model to assess the possible neuroprotective effects of central acting calcium channel blockers using a nondegradable sustained-release device has been developed (3). In this model an intraocular infusion was used to elevate the intraocular pressure (IOP). To assess the effects of the study drug, IOP was maintained at 40mmHg for over an hour in both treatment and control eyes and was then decreased to a normal level. The procedure was repeated at 48 and 72 hours to simulate IOP spikes in human eyes (3). 

Nondegradable Intraocular Sustained-Release Drug Delivery Devices... 

While a number of animal models of diabetic macular edema exist, sustained delivery of steroids using a nondegradable device has not been tested in an animal model (14,15). Other nondegradable sustained-release drugs that have been investigated in vitro but not in animal models, include methotrexate and trimetrexate to treat intraocular lymphoma, and disease 2-methoxyestradiol to treat choroidal neovascularization (16 18). 

After three and six weeks, implants in gas-filled eyes had smaller amounts of drug than implants in eyes without gas. The authors hypothesized that this discrepancy was due to an increased drug clearance rate in gas-filled eyes secondary to transient disruption of the blood-retinal barrier caused by the intravitreal injection of C3F8 gas. Maintenance of the steady-state level would then require a higher rate of drug release from implants in the gas-filled eyes. If this hypothesis is true then nondegradable sustained-release drug devices may have a shorter lifespan in gas-filled eyes (27). 

In view of successful animal experiments (20 see also Chapter 14), a sustained-release dexamethasone device was implanted in one eye of a patient with bilateral severe uveitis associated with multiple sclerosis (20,21). The patient had previously undergone pars plana lensectomy and vitrectomy in the right eye for decreased vision associated with cataract. Despite chronic topical corticosteroids, the patient had persistent bilateral low-grade inflammation and recurrent severe bilateral iridocyclitis. Best corrected visual acuity was 20/400 in both eyes. Systemic corticosteroids and methotrexate controlled the intraocular inflammation but the patient was intolerant of these medications because of systemic side effects. The nondegradable dexamethasone device was inserted into the patient s left eye. 

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