Adjuvant Chemotherapy for Brain Tumors Delivered via a Novel Intra-Cavity Moldable Polymer Matrix

<div><p>Introduction</p><p>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.</p> <p>Methods</p><p>PLGA/PEG microparticle-based matrices were molded around an <i>ex</i><i>vivo</i> brain pseudo-resection cavity and analyzed using magnetic resonance imaging and computerized tomography. <i>In</i><i>vitro</i> 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.</p> <p>Results</p><p>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 <i>in</i><i>vitro</i>. Trichostatin A, etoposide and methotrexate were released from the matrices over a 3-4 week period <i>in</i><i>vitro</i> and etoposide released over 3 days <i>in</i><i>vivo</i>, 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 <i>in</i><i>vitro</i> suggesting good biocompatibility <i>in</i><i>vivo</i>. Active trichostatin A, etoposide and methotrexate can be incorporated and released gradually from matrices, with radiotherapy unlikely to interfere with release.</p> <p>Conclusion</p><p>The PLGA/PEG delivery system offers an innovative intra-cavity approach to administer chemotherapeutics for improved local control of malignant brain tumors.</p>