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Abstract
Carboplatin is a potent anticancer agent that has shown efficacy in clinical trials against malignant glioma, one of the most deadly cancers in humans. However, a high systemic dose is required to achieve an effective concentration in the brain because of the presence of the blood-brain barrier (BBB). Such a high dose can cause many side effects. Local delivery of antitumor agents to the brain using injectable and biodegradable microspheres is a new strategy for the treatment of malignant glioma. This method is able to bypass the BBB and allows maximal local exposure and minimal systemic exposure to avoid the severe side effects of carboplatin. Delivering sustained-release microspheres directly to the tumor site could also control local tumor recurrence and improve survival. In the present studies, carboplatin-loaded microspheres were delivered intracerebrally in rats. No signs of systemic or neurologic toxicity associated with the microspheres implanted in the rat brain were observed. The in vivo release of carboplatin followed apparently zero-order release kinetics up to 30 days. The surface characteristics of the microspheres retrieved from the rat brains changed with the progress of polymer biodegradation. Implantation of the microspheres evoked a transient and localized inflammatory reaction that was well tolerated by the animals.