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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.

Authors

STUART SMITH stuart.smith@nottingham.ac.uk
Clinical Associate Professor

Cheryl V. Rahman

Alison A. Ritchie

Toby W. Gould

Jennifer H. Ward

RICHARD GRUNDY richard.grundy@nottingham.ac.uk
Professor of Paediatric Neuro-Oncology

Philip A. Clarke



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.

Journal Article Type Article
Publication Date Oct 1, 2014
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
APA6 Citation Smith, S. J., Rahman, C. V., Ritchie, A. A., Gould, T. W., Ward, J. H., Shakesheff, K. M., …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
DOI https://doi.org/10.1308/003588414X13946184903568
Keywords Glioblastoma, Drug Delivery Systems, Neurosurgery
Publisher URL http://publishing.rcseng.ac.uk/doi/10.1308/003588414X13946184903568
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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