Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model

Jeane Chen, Sarah B. White, Kathleen R. Harris, Weiguo Li, Jonathan W.T. Yap, Dong-Hyun Kim, Robert J Lewandowski, Lonnie D. Shea, Andrew Christian Larson*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-. co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 h. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors.

Original languageEnglish (US)
Pages (from-to)299-306
Number of pages8
JournalBiomaterials
Volume61
DOIs
StatePublished - Aug 1 2015

Keywords

  • Hepatocellular carcinoma
  • Magnetic resonance imaging
  • Poly(lactide-co-glycolide)
  • Sorafenib

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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