Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model. Biomaterials 2015 Aug;61:299-306
Date
05/30/2015Pubmed ID
26022791Pubmed Central ID
PMC4498403DOI
10.1016/j.biomaterials.2015.05.010Scopus ID
2-s2.0-84939163121 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
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.
Author List
Chen J, White SB, Harris KR, Li W, Yap JW, Kim DH, Lewandowski RJ, Shea LD, Larson ACAuthor
Sarah B. White MD, MS, FSIR, FCIRSE Associate Dean, Vice Chair, Professor in the Radiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Capsules
Cell Line, Tumor
Contrast Media
Diffusion
Drug Monitoring
Ferric Compounds
Liver Neoplasms
Magnetic Resonance Imaging
Niacinamide
Particle Size
Phenylurea Compounds
Polyglactin 910
Rabbits