- Title
- Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma
- Creator
- Arms, Lauren M.; Duchatel, Ryan J.; Jackson, Evangeline R.; Sobrinho, Pedro Garcia; Dun, Matthew D.; Hua, Susan
- Relation
- Journal of Controlled Release Vol. 370, Issue June 2024, p. 835-865
- Publisher Link
- http://dx.doi.org/10.1016/j.jconrel.2024.05.018
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2024
- Description
- 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.
- Subject
- diffuse intrinsic pontine glioma; diffuse midline glioma; brain cancer; blood-brain barrier; drug delivery; pharmaceutics
- Identifier
- http://hdl.handle.net/1959.13/1504474
- Identifier
- uon:55532
- Identifier
- ISSN:0168-3659
- Rights
- x
- Language
- eng
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