Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma

Lauren M Arms; Ryan J Duchatel; Evangeline R Jackson; Pedro Garcia Sobrinho; Matthew D Dun; Susan Hua

doi:10.1016/j.jconrel.2024.05.018

Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma

J Control Release. 2024 May 20:370:835-865. doi: 10.1016/j.jconrel.2024.05.018. Online ahead of print.

Authors

Lauren M Arms¹, Ryan J Duchatel², Evangeline R Jackson², Pedro Garcia Sobrinho³, Matthew D Dun², Susan Hua⁴

Affiliations

¹ Therapeutic Targeting Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia; Paediatric Program, Mark Hughes Foundation Centre for Brain Cancer Research, College of Health, Medicine & Wellbeing, University of Newcastle, Callaghan, NSW, Australia.
² Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Paediatric Program, Mark Hughes Foundation Centre for Brain Cancer Research, College of Health, Medicine & Wellbeing, University of Newcastle, Callaghan, NSW, Australia.
³ Therapeutic Targeting Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
⁴ Therapeutic Targeting Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia; Paediatric Program, Mark Hughes Foundation Centre for Brain Cancer Research, College of Health, Medicine & Wellbeing, University of Newcastle, Callaghan, NSW, Australia. Electronic address: Susan.Hua@newcastle.edu.au.

PMID: 38744345
DOI: 10.1016/j.jconrel.2024.05.018

Abstract

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), is the primary cause of brain tumor-related death in pediatric patients. DIPG is characterized by a median survival of <12 months from diagnosis, harboring the worst 5-year survival rate of any cancer. Corticosteroids and radiation are the mainstay of therapy; however, they only provide transient relief from the devastating neurological symptoms. Numerous therapies have been investigated for DIPG, but the majority have been unsuccessful in demonstrating a survival benefit beyond radiation alone. Although many barriers hinder brain drug delivery in DIPG, one of the most significant challenges is the blood-brain barrier (BBB). Therapeutic compounds must possess specific properties to enable efficient passage across the BBB. In brain cancer, the BBB is referred to as the blood-brain tumor barrier (BBTB), where tumors disrupt the structure and function of the BBB, which may provide opportunities for drug delivery. However, the biological characteristics of the brainstem's BBB/BBTB, both under normal physiological conditions and in response to DIPG, are poorly understood, which further complicates treatment. Better characterization of the changes that occur in the BBB/BBTB of DIPG patients is essential, as this informs future treatment strategies. Many novel drug delivery technologies have been investigated to bypass or disrupt the BBB/BBTB, including convection enhanced delivery, focused ultrasound, nanoparticle-mediated delivery, and intranasal delivery, all of which are yet to be clinically established for the treatment of DIPG. Herein, we review what is known about the BBB/BBTB and discuss the current status, limitations, and advances of conventional and novel treatments to improving brain drug delivery in DIPG.

Keywords: Blood-brain barrier; Brain cancer; Diffuse intrinsic pontine glioma; Diffuse midline glioma; Drug delivery; Pharmaceutics.

Publication types

Review