The unsatisfactory therapeutic outcome for glioma is mainly due to the poor blood-brain barrier (BBB) permeability and inefficient accumulation in the glioma area of chemotherapeutic agents. The existing drug delivery strategies can increase drug transport to the brain but are restricted by side effects and/or poor delivery efficiency. In this study, potent brain penetration enhancers were screened from the active components of aromatic resuscitation drugs used in traditional Chinese medicine. A novel glioma-targeting system based on enhancer-modified albumin nanoparticles was developed to safely and efficiently deliver drugs to the glioma regions in the brain. The nanoparticles improved the transport of nanoparticles across brain capillary endothelial cell (BCEC) monolayer by increasing endocytosis in endothelial cells and causing BBB disruption. In vivo imaging studies demonstrated that the systems could enter the brain and subsequently accumulate in glioma cells with a much higher targeting efficiency than that of transferrin-modified albumin nanoparticles. Of note, the nanoparticles could be captured and penetrate through endothelial cells fenestrae in pineal gland, which is suggestive of an effective way to deliver a nanosystem to the brain by bypassing the BBB. The nanoparticles showed good biocompatibility and negligible cytotoxicity. The results reveal an efficient and safe strategy for brain drug delivery in glioma therapy.
Keywords: BBB-disrupting; brain penetration enhancer; brain permeability; glioma; menthol; pineal gland.