title: Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model.
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.
authors.affiliation: Department of Chemical & Biological Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Radiology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Jeane
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Department of Vascular and Interventional Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: White
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Harris
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Research Resource Center, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Jonathan W T
authors.initials: JW
authors.lastname: Yap
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lewandowski
authors.affiliation: Department of Chemical & Biological Engineering, Northwestern University, Evanston, IL 60208, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA; Department of Biomedical Engineering, Northwestern University, Chicago, IL 60611, USA; Department of Electrical Engineering and Computer Science, Evanston, IL 60208, USA. Electronic address: a-larson@northwestern.edu.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D003287:Contrast Media; D004058:Diffusion; D016903:Drug Monitoring / Q000379:methods; D005290:Ferric Compounds; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D010316:Particle Size; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry; D011098:Polyglactin 910 / Q000008:administration & dosage / Q000737:chemistry*; D011817:Rabbits; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D003287:Contrast Media; D005290:Ferric Compounds; D010671:Phenylurea Compounds; C000499:ferric oxide; D009536:Niacinamide; D011098:Polyglactin 910; D000077157:Sorafenib
keywords: Hepatocellular carcinoma; Magnetic resonance imaging; Poly(lactide-co-glycolide); Sorafenib