Regulation of pathological blood-brain barrier for intracranial enhanced drug delivery and anti-glioblastoma therapeutics
Kai Wang, Fengtian Zhang, CHANGLONG WEN, ZHIHUA HUANG, ZHIHAO HU, YUWEN ZHANG, FUQIANG HU, Lijuan Wen
Abstract
The blood-brain barrier (BBB) is an essential component in regulating and maintaining the homeostatic microenvironment of the central nervous system (CNS). During the occurrence and development of glioblastoma (GBM), BBB is pathologically destroyed with a marked increase in permeability. Due to the obstruction of the BBB, current strategies for GBM therapeutics still obtain a meager success rate and may lead to systemic toxicity. Moreover, chemotherapy could promote pathological BBB functional restoration, which results in significantly reduced intracerebral transport of therapeutic agents during multiple administrations of GBM and the eventual failure of GBM chemotherapy. The effective delivery of intracerebral drugs still faces severe challenges. However, strategies that regulate the pathological BBB to enhance the transport of therapeutic agents across the barrier may provide new opportunities for the effective and safe treatment of GBM. This article reviews the structure and function of BBB in physiological states, the mechanisms underlying BBB pathological fenestration during the development of GBM, and the therapeutic strategies of GBM based on BBB intervention and medicinal drugs transporting across the BBB.