Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Smith, Stuart J.; Rahman, Cheryl V.; Ritchie, Alison A.; Gould, Toby W.; Ward, Jennifer H.; Shakesheff, Kevin M.; Grundy, Richard G.; Rahman, Ruman; Clarke, Philip A.

Abstract

Introduction: The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.
Methods: Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.
Results: Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.
Conclusions: Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.

Citation

Smith, S. J., Rahman, C. V., Ritchie, A. A., Gould, T. W., Ward, J. H., Shakesheff, K. M., Grundy, R. G., Rahman, R., & Clarke, P. A. (2014). Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma. Annals of The Royal College of Surgeons of England, 96(7), 495-501. https://doi.org/10.1308/003588414X13946184903568

• Journal Article Type: Article
• Acceptance Date: Feb 14, 2014
• Online Publication Date: Mar 11, 2015
• Publication Date: Oct 1, 2014
• Deposit Date: Feb 17, 2016
• Publicly Available Date: Feb 17, 2016
• Journal: Annals of the Royal College of Surgeons of England
• Print ISSN: 0035-8843
• Electronic ISSN: 1478-7083
• Publisher: Royal College of Surgeons of England
• Peer Reviewed: Peer Reviewed
• Volume: 96
• Issue: 7
• Pages: 495-501
• DOI: https://doi.org/10.1308/003588414X13946184903568
• Keywords: Glioblastoma, Drug Delivery Systems, Neurosurgery
• Public URL: https://nottingham-repository.worktribe.com/output/734877
• Publisher URL: http://publishing.rcseng.ac.uk/doi/10.1308/003588414X13946184903568
• Contract Date: Feb 17, 2016