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

Christopher C Parkins; Joseph H McAbee; Lisa Ruff; Astrid Wendler; Richard Mair; Richard J Gilbertson; Colin Watts; Oren A Scherman

doi:10.1016/j.biomaterials.2021.120919

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

Biomaterials. 2021 Sep:276:120919. doi: 10.1016/j.biomaterials.2021.120919. Epub 2021 May 28.

Authors

Christopher C Parkins¹, Joseph H McAbee², Lisa Ruff³, Astrid Wendler³, Richard Mair³, Richard J Gilbertson³, Colin Watts⁴, Oren A Scherman⁵

Affiliations

¹ Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom.
² Department of Clinical Neurosciences, Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, UK; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
³ Department of Clinical Neurosciences, Division of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK.
⁴ Department of Clinical Neurosciences, Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, UK; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, Brain Cancer Program, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
⁵ Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom. Electronic address: oas23@cam.ac.uk.

PMID: 34419838
DOI: 10.1016/j.biomaterials.2021.120919

Abstract

Peptide functionalized hyaluronic acid (HA_CF) 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.

Keywords: Cucurbit[8]uril; Drug-delivery; Glioblastoma; Hyaluronic acid; Hydrogel; Rheology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
Drug Delivery Systems
Glioblastoma* / drug therapy
Humans
Hyaluronic Acid
Hydrogels
Mice
Rheology

Substances

Hydrogels
Hyaluronic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding