<p>Nanoparticle Drug Delivery System for Glioma and Its Efficacy Improvement Strategies: A Comprehensive Review</p>

Abstract

Gliomas are the most common tumor of the central nervous system. However, the presence of the brain barrier blocks the effective delivery of drugs and leads to the treatment failure of various drugs. The development of a nanoparticle drug delivery system (NDDS) can solve this problem. In this review, we summarized the brain barrier (including bloodbrain barrier (BBB), blood-brain tumor barriers (BBTB), brain-cerebrospinal fluid barrier (BCB), and nose-to-brain barrier), NDDS of glioma (such as passive targeting systems, active targeting systems, and environmental responsive targeting systems), and NDDS efficacy improvement strategies and deficiencies. The research prospect of drug-targeted delivery systems for glioma is also discussed.

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

“…Brain distribution can be facilitated by nanotechnology [ 150 ]. Studies have shown that nanotherapeutics and nanomaterials improve the biodistribution of drugs in the brain for more efficient treatment of glioblastoma, not only via convection-enhanced delivery [ 151 ] but also via intranasal delivery [ 152 ].…”

“…Chemotherapeutic agents are in general considered for INDD systems [152,153]. The main advantage of the IN route is the chance of reduced side effects in other organ systems [146,154].…”

“…They facilitate a more targeted and efficient brain delivery and reduce side effects at the same time [223]. The advantage of using nanotechnology-based drug delivery systems has been shown for different CNS indications, such as epilepsy, psychosis-related disorders and glioma [152,[223][224][225][226][227].…”

Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors

“…In order to selectively act drugs on the lesions and reduce the impact on peripheral tissues, a brain drug delivery system needs to be established. Osmotic BBB disruption based on intra-arterial infusion of hypertonic mannitol solution, intravenous bradykinin analogs that relax tight junctions, drugs coupling to a mediator targeting and shuttling insulin or transferrin receptors, nanoparticle drug delivery system, and direct delivery of drugs to the brain parenchyma or excision cavity are potential methods for metabolic immunotherapeutic drugs to cross BBTB ( van Tellingen et al, 2015 ; Li et al, 2020 ). Targeting metabolic functional proteins selectively and highly expressed in glioma cells, such as GLUT3 ( Xu et al, 2015 ; Zheng et al, 2016 ), or using targeted metabolic drug delivery systems based on neutrophils ( Osuka and Van Meir, 2017 ; Xue et al, 2017 ) or other immune cells accumulating in glioma tissues is also a good solution.…”

Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery

“…This strictly limited selection imposes a great challenge on glioma treatment. To overcome this issue, various nanoparticulate platforms have been widely investigated to develop BBB-penetrating delivery systems because of their great clinical potential in cancer diagnosis and treatment [4][5][6]. These nanoplatforms can be exploited as imaging agents to guide the maximal surgical resection, drug carriers to improve chemotherapy, or theranostic systems to achieve imaging-guided drug delivery and therapy monitoring [7][8][9][10][11].…”