Mechanically matching the rheological properties of brain tissue for drug-delivery in human glioblastoma models.

Change log
Parkins, Christopher C 
McAbee, Joseph H 
Ruff, Lisa 
Wendler, Astrid 
Mair, Richard 

Peptide functionalized hyaluronic acid (HACF) cross-linked by cucurbit[8]uril (CB[8]), a new class of drug-delivery reservoirs, is used to enable improved drug bioavailability for glioblastoma tumors in patient-derived xenograft (PDX) models. The mechanical and viscoelastic properties of native human and mouse tissues are measured over 8 h via oscillatory rheology under physiological conditions. Treatment with drug-loaded hydrogels allowed for a significant survival impact of 45 % (55.5-80.5 days). A relationship between the type of PDX tumor formed-a consequence of the heterogeneic nature of GB tumors-and changes in the initial survival is observed owing to greater local pressure from stiffer tumors. These biocompatible and tailorable materials warrant use as drug delivery reservoirs in PDX resection models, where the mechanical properties can be readily adjusted to match the stiffness of local tissue and thus have potential to improve the survival of GB patients.

Cucurbit[8]uril, Drug-delivery, Glioblastoma, Hyaluronic acid, Hydrogel, Rheology, Animals, Brain, Drug Delivery Systems, Glioblastoma, Humans, Hyaluronic Acid, Hydrogels, Mice, Rheology
Journal Title
Conference Name
Journal ISSN
Volume Title
Elsevier BV
Cancer Research UK (C14303/A17197)
Cancer Research UK (C9685/A20760)
Cancer Research UK (26398)
Cancer Research UK (22492)
Engineering and Physical Sciences Research Council (EP/S009000/1)
EPSRC Doctoral Training Grant, EPSRC reference EP/M508007/1 for lead author Chris Parkins. This work was supported by The Brain Tumour Charity (GN-000409), the National Institute for Health Research Cambridge Biomedical Research Centre and the Higher Education Funding Council for England. We acknowl- edge the Human Research Tissue Bank and Biomedical Research Centre for a portion of the tissue being accessed. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. CCP is thankful for the support of the EPSRC and the Brain Tumour Charity for funding. JHM acknowledges the support of the Gates Cambridge Trust and NIH OxCam Scholarship programme. LR and RJG thank the Mathile Family Foundation for funding.