Biocompatibility study of glycofurol in rat brains

Glycofurol (GF) has been used clinically as a solvent for parenteral drug delivery systems. However, the application and toxicity of GF in the brain have not been reported. This study was carried out to assess the systemic and neurologic reactions of GF in rats upon intracranial injection. Hematological and neuropathological assessments of rats were performed during the acute, subacute and chronic period after the injection. Injection of the GF solution (GF 25 mu L + PBS 25 mu L) into the brain cortex showed that it did not cause any deaths or clinical neurobehavioral abnormalities. At the same volume as phosphate-buffered saline (PBS) injection, it had mild effects on all hematological data and histopathology of brain tissues. Nevertheless, histomorphologic assessments of the brain tissues treated with PBS 70 mu L revealed different tissue responses compared with those of 70 mu L GF solution (30 mu L + PBS 40 mu L) where tissues around the administration site showed elevated polymorphonuclear leukocytes, macrophages and gliosis. These results demonstrated that the GF solution (GE 25 mu L PBS 25 mu L) administration was well tolerated and caused minor inflammatory responses of cerebral cortex. This suggests possibilities of GE for drug delivery systems in the brain parenchymal tissues.