Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profil...

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Veröffentlicht in:Cardiovascular and interventional radiology 2010-06, Vol.33 (3), p.576-582
Hauptverfasser: Lee, Kwang-Hun, Liapi, Eleni A., Cornell, Curt, Reb, Philippe, Buijs, Manon, Vossen, Josephina A., Ventura, Veronica Prieto, Geschwind, Jean-Francois H.
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container_end_page 582
container_issue 3
container_start_page 576
container_title Cardiovascular and interventional radiology
container_volume 33
creator Lee, Kwang-Hun
Liapi, Eleni A.
Cornell, Curt
Reb, Philippe
Buijs, Manon
Vossen, Josephina A.
Ventura, Veronica Prieto
Geschwind, Jean-Francois H.
description The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82–94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study’s end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.
doi_str_mv 10.1007/s00270-010-9794-1
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In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study’s end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. 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source MEDLINE; SpringerNature Journals
subjects Acrylic Resins
Angiography, Digital Subtraction
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
ARTERIES
BLOOD VESSELS
BODY
Cardiology
CARDIOVASCULAR SYSTEM
Chemoembolization, Therapeutic - instrumentation
Contrast Media
COPOLYMERS
DIGESTIVE SYSTEM
Disease Models, Animal
DISEASES
DOXORUBICIN
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
DRUGS
GLANDS
Hepatic Artery
Imaging
Laboratory Investigation
LIVER
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
Male
MAMMALS
Medicine
Medicine & Public Health
MICROSPHERES
NEOPLASMS
Nuclear Medicine
ORGANIC COMPOUNDS
ORGANIC POLYMERS
ORGANS
POLYMERS
Polyvinyls
RABBITS
Radiology
RADIOLOGY AND NUCLEAR MEDICINE
Ultrasound
VERTEBRATES
title Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer
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