Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours

McCrorie, Phoebe; Mistry, Jatin; Taresco, Vincenzo; Lovato, Tatiana; Fay, Michael; Ward, Ian; Ritchie, Alison A.; Clarke, Philip A.; Smith, Stuart J.; Marlow, Maria; Rahman, Ruman

Abstract

Glioblastoma is a malignant brain tumour with a median survival of 14.6 months from diagnosis. Despite maximal surgical resection and concurrent chemoradiotherapy, reoccurrence is inevitable. To try combating the disease at a stage of low residual tumour burden immediately post-surgery, we propose a localised drug delivery system comprising of a spray device, bioadhesive hydrogel (pectin) and drug nanocrystals coated with polylactic acid-polyethylene glycol (NCPPs), to be administered directly into brain parenchyma adjacent to the surgical cavity. We have repurposed pectin for use within the brain, showing in vitro and in vivo biocompatibility, bio-adhesion to mammalian brain and gelling at physiological brain calcium concentrations. Etoposide and olaparib NCPPs with high drug loading have shown in vitro stability and drug release over 120 h. Pluronic F127 stabilised NCPPs to ensure successful spraying, as determined by dynamic light scattering and transmission electron microscopy. Successful delivery of Cy5-labelled NCPPs was demonstrated in a large ex vivo mammalian brain, with NCPP present in the tissue surrounding the resection cavity. Our data collectively demonstrates the pre-clinical development of a novel localised delivery device based on a sprayable hydrogel containing therapeutic NCPPs, amenable for translation to intracranial surgical resection models for the treatment of malignant brain tumours.

Citation

McCrorie, P., Mistry, J., Taresco, V., Lovato, T., Fay, M., Ward, I., Ritchie, A. A., Clarke, P. A., Smith, S. J., Marlow, M., & Rahman, R. (2020). Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours. European Journal of Pharmaceutics and Biopharmaceutics, 157, 108-120. https://doi.org/10.1016/j.ejpb.2020.10.005

• Journal Article Type: Article
• Acceptance Date: Oct 11, 2020
• Online Publication Date: Oct 14, 2020
• Publication Date: 2020-12
• Deposit Date: Oct 16, 2020
• Publicly Available Date: Oct 15, 2021
• Journal: European Journal of Pharmaceutics and Biopharmaceutics
• Print ISSN: 0939-6411
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 157
• Pages: 108-120
• DOI: https://doi.org/10.1016/j.ejpb.2020.10.005
• Keywords: Biotechnology; Pharmaceutical Science; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4968843
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S0939641120303052?via%3Dihub