Research Repository

See what's under the surface

Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix

Rahman, Cheryl V.; Smith, Stuart J.; Morgan, Paul S.; Langmack, Keith A.; Clarke, Phil A.; Ritchie, Alison A.; Macarthur, Donald C.; Rose, Felicity R.A.J.; Shakesheff, Kevin M.; Grundy, Richard G.; Rahman, Ruman

Authors

Cheryl V. Rahman

Stuart J. Smith

Paul S. Morgan

Keith A. Langmack

Phil A. Clarke

Alison A. Ritchie

Donald C. Macarthur

Felicity R.A.J. Rose

Richard G. Grundy

Ruman Rahman

Abstract

INTRODUCTION

Polymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility, toxicity and sustained drug release capability of a novel formulation of poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) microparticles.

METHODS

PLGA/PEG microparticle-based matrices were molded around an ex vivo brain pseudo-resection cavity and analyzed using magnetic resonance imaging and computerized tomography. In vitro toxicity of the polymer was assessed using tumor and endothelial cells and drug release from trichostatin A-, etoposide- and methotrexate-loaded matrices was determined. To verify activity of released agents, tumor cells were seeded onto drug-loaded matrices and viability assessed.

RESULTS

PLGA/PEG matrices can be molded around a pseudo-resection cavity wall with no polymer-related artifact on clinical scans. The polymer withstands fractionated radiotherapy, with no disruption of microparticle structure. No toxicity was evident when tumor or endothelial cells were grown on control matrices in vitro. Trichostatin A, etoposide and methotrexate were released from the matrices over a 3-4 week period in vitro and etoposide released over 3 days in vivo, with released agents retaining cytotoxic capabilities. PLGA/PEG microparticle-based matrices molded around a resection cavity wall are distinguishable in clinical scanning modalities. Matrices are non-toxic in vitro suggesting good biocompatibility in vivo. Active trichostatin A, etoposide and methotrexate can be incorporated and released gradually from matrices, with radiotherapy unlikely to interfere with release.

CONCLUSION

The PLGA/PEG delivery system offers an innovative intra-cavity approach to administer chemotherapeutics for improved local control of malignant brain tumors.

Journal Article Type Article
Publication Date Oct 14, 2013
Journal PloS one
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 8
Issue 10
Article Number e77435
Institution Citation Rahman, C. V., Smith, S. J., Morgan, P. S., Langmack, K. A., Clarke, P. A., Ritchie, A. A., …Rahman, R. (2013). Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix. PLoS ONE, 8(10), doi:10.1371/journal.pone.0077435
DOI https://doi.org/10.1371/journal.pone.0077435
Publisher URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077435
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

Files

PLoS ONE 2013 Rahman.pdf (1.5 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




Downloadable Citations