Local delivery of poly lactic-co-glycolic acid microspheres containing imatinib mesylate inhibits intracranial xenograft glioma growth

Ofra Benny, Lata G. Menon, Gilert Ariel, Effrat Goren, Seung Ki Kim, Chaney Stewman, Peter M. Black, Rona S. Carroll, Marcelle Machluf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Purpose: In an effort to develop new therapeutic strategies to treat malignant gliomas, we have designed poly (lactic-co-glycolic) acid (PLGA) microparticles that deliver imatinib mesylate, a small molecule tyrosine kinase inhibitor. The local continuous release of imatinib mesylate at the tumor site overcomes many obstacles associated with systemic delivery. Experimental Design: Polymeric microspheres were prepared from various compositions of PLGA and loaded with imatinib mesylate. Imatinib release profiles, biological activity, and effect on PDGFR-B phosphorylation were confirmed in vitro. The therapeutic efficacy of imatinib microspheres was examined in two s,c, and orthotopic human glioblastoma xenograft models. Results: A single local injection of PLGA microspheres loaded with a low concentration of imatinib mesylate led to 88% and 79% reduction in s.c. human (U87-MG) and murine (GL261) glioma tumors, respectively PLGA-imatinib mesylate administered intracranially led to a 79% reduction in U87MG tumor volume. Immunohistochemical analysis showed a marked decrease in proliferation indicesand tumor vessel density in the s.c, modeland induction of apoptosisin an intracranial model. Conclusion: This is the first study to show the therapeutic efficacy of the local delivery of imatinib mesylate using a polymeric delivery system.

Original languageAmerican English
Pages (from-to)1222-1231
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number4
DOIs
StatePublished - 15 Feb 2009
Externally publishedYes

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