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Adv Healthc Mater. 2019 Feb;8(3):e1801391. doi: 10.1002/adhm.201801391. Epub 2019 Jan 11.

Designing Next-Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic.

Author information

1
Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
2
Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK.
3
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
4
Department of Neurosurgery, Birmingham Brain Cancer Program, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.

Abstract

To date, the clinical outcomes and survival rates for patients with glioblastoma (GB) remain poor. A promising approach to disease-modification involves local delivery of adjuvant chemotherapy into the resection cavity, thus circumventing the restrictions imposed by the blood-brain barrier. The clinical performance of the only FDA-approved local therapy for GB [carmustine (BCNU)-loaded polyanhydride wafers], however, has been disappointing. There is an unmet medical need in the local treatment of GB for drug delivery vehicles that provide sustained local release of small molecules and combination drugs over several months. Herein, key quantitative lessons from the use of local and systemic adjuvant chemotherapy for GB in the clinic are outlined, and it is discussed how these can inform the development of next-generation therapies. Several recent approaches are highlighted, and it is proposed that long-lasting soft materials can capture the value of stiff BCNU-loaded wafers while addressing a number of unmet medical needs. Finally, it is suggested that improved communication between materials scientists, biomedical scientists, and clinicians may facilitate translation of these materials into the clinic and ultimately lead to improved clinical outcomes.

KEYWORDS:

adjuvant chemotherapy; glioblastoma; local drug delivery; soft biomaterials

PMID:
30632715
DOI:
10.1002/adhm.201801391
[Indexed for MEDLINE]

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