The safety and effectiveness of systemic and topical medical therapies for ocular disorders are limited due to poor ocular drug uptake, nonspecificity to target tissues, systemic side effects, and poor adherence to therapy. Intravitreal injections can enhance ocular drug delivery, but the need for frequent retreatment and potential injection-related side effects limit the utility of this technique. Sustained-release drug delivery systems have been developed to overcome these limitations; such systems can achieve prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure and side effects and improving patient adherence to therapy. A critical factor in the development of safe and effective drug delivery systems has been the development of biocompatible polymers, which offer the versatility to tailor drug release kinetics for specific drugs and ocular diseases. Ocular implants include nonbiodegradable and biodegradable designs, with the latter offering several advantages. The polymers most commonly used in biodegradable delivery systems are synthetic aliphatic polyesters of the poly-α-hydroxy acid family including polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid. The characteristics of these polymers for medical applications as well as the pharmacological properties, safety, and clinical effectiveness of biodegradable drug implants for the treatment of ocular diseases are reviewed herein.

Objective. To examine the influence of superoxide on the severity of collagen-induced arthritis (CIA) in mice.Methods. CIA was induced in DBA/1J mice lacking the extracellular superoxide dismutase (EC-SOD) gene (knockout [KO]) and in normal DBA/1J mice (wild-type [WT]).Results. The clinical disease activity score was significantly higher in EC-SOD-KO mice than in WT mice between days 36 and 53, and the histologic scores for joint damage on day 53 increased 2-fold or more in the EC-SOD-KO mice. There were no significant differences between the 2 groups of mice in proliferation indices of spleen or lymph node cells in vitro after stimulation with type II collagen. Although both IgG1 and IgG2a anticollagen antibody levels increased in both groups of mice between days 21 and 53, there were no significant differences between the 2 groups. Lipopolysaccharide-stimulated spleen cells from EC-SOD-KO mice produced greater levels of tumor necrosis factor ␣ (TNF␣) over 48 hours in culture compared with cells from WT mice. Increased steady-state levels of messenger RNA (mRNA) for interferon-␥ (IFN␥), TNF␣, and interleukin-1␤ (IL-1␤), and lower levels of IL-1 receptor antagonist (IL-1Ra) mRNA were present in the joints of the EC-SOD-KO mice compared with the WT mice.Conclusion. The absence of EC-SOD leads to more severe CIA, which may be accompanied by enhanced production of the proinflammatory cytokines IFN␥, TNF␣, and IL-1␤, and decreased production of the antiinflammatory cytokine IL-1Ra in the joints.

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