Direct intracerebral delivery of carboplatin from PLGA microspheres against experimental malignant glioma in rats

Abstract

There has been an increasing interest in intracerebral delivery of anticancer agents using biodegradable polymers for the treatment of malignant glioma. This approach circumvents the blood-brain barrier (BBB) to achieve a high local drug concentration in the brain tumor sites and minimize side effects associated with a high systemic dose. It could also control local tumor recurrence and improve survival. In order to deliver anticancer drugs intracerebrally from polymers to tumor sites with minimal surgery, injectable poly(d,l-lactic-coglycolic acid) (PLGA) microspheres impregnated with carboplatin have been prepared. In the current studies, the brain tissue reaction to blank or carboplatin-loaded PLGA microspheres was investigated in rats. The PLGA microspheres were well tolerated by all of the rats. The brain tissue reaction to the blank microspheres was accompanied by mild edema, and macrophage/astrocyte/microglia proliferation. The tissue reaction to the carboplatin microspheres was characterized as edema, necrosis, and a more pronounced phagocytic inflammatory reaction. The observed inflammatory reactions decreased remarkably after 1 month. Carboplatin microspheres were then implanted intracerebrally in the rat glioma models. Higher drug concentrations were achieved in the brain tumor than in normal tissues. The survival and weight loss of the rats receiving carboplatin microspheres were compared with those of the rats receiving systemic doses. The local treatment was more effective in controlling the weight loss of the tumor-bearing rats, and was as effective as the systemic treatment in prolonging survival.