title: Sorafenib and 2,3,5-triiodobenzoic acid-loaded imageable microspheres for transarterial embolization of a liver tumor.
abstract: Sorafenib (SOF; an angiogenesis inhibitor) and 2,3,5-triiodobenzoic acid (TIBA; a contrast agent for computed tomography imaging)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated. Embolization, drug delivery, and tracing the distribution of MSs for liver cancer therapy were accomplished with the developed MSs after their intra-arterial (IA) administration. SOF/TIBA/PLGA MSs with 24.8-28.5 µm mean diameters were prepared, and the sustained release of SOF from MSs was observed. Lower systemic exposure (represented as the area under the curve [AUC]) and maximum drug concentration in plasma (Cmax) values of the SOF/TIBA/PLGA MSs group (IA administration, 1 mg/kg) in the results of the pharmacokinetic study imply alleviated unwanted systemic effects (e.g., hand and foot syndrome), compared to the SOF solution group (oral administration, 10 mg/kg). In a rat hepatoma model, the increase of microvessel density (MVD) following arterial embolization (i.e., reactive angiogenesis) was partially limited by SOF/TIBA/PLGA MSs. This resulted in the SOF/TIBA/PLGA MSs group (IA administration, single dosing, 1 mg/kg) showing a smaller tumor size increase and viable tumor portion compared to the TIBA/PLGA MSs group. These findings suggest that a developed SOF/TIBA/PLGA MS can be a promising therapeutic system for liver cancer using a transarterial embolization strategy.
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Ju-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Cho
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea. angiointervention@gmail.com.
authors.forename: Hyo-Cheol
authors.initials: HC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea. hjcho@kangwon.ac.kr.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000737:chemistry; D016461:Chemoembolization, Therapeutic / Q000379:methods; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D065546:Drug Liberation; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D000077157:Sorafenib; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014283:Triiodobenzoic Acids / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D010671:Phenylurea Compounds; D014283:Triiodobenzoic Acids; D009536:Niacinamide; D000077157:Sorafenib; C052968:2,3,5-triiodobenzoic acid