Abstract
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.
Similar content being viewed by others
References
de Luis E, Bilbao JI, de Ciercoles JA, Martinez-Cuesta A, de Martino Rodriguez A, Lozano MD (2008) In vivo evaluation of a new embolic spherical particle (HepaSphere) in a kidney animal model. CardioVasc Interv Radiol 31(2):367–376
Gonzalez MV, Tang Y, Phillips GJ et al (2008) Doxorubicin eluting beads-2: methods for evaluating drug elution and in-vitro:in-vivo correlation. J Mater Sci Mater Med 19(2):767–775
Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF (2006) New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 12(8):2563–2567
Lewis AL, Gonzalez MV, Leppard SW et al (2007) Doxorubicin eluting beads 1: effects of drug loading on bead characteristics and drug distribution. J Mater Sci Mater Med 18(9):1691–1699
Lewis AL, Taylor RR, Hall B, Gonzalez MV, Willis SL, Stratford PW (2006) Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol 17(8):1335–1343
Jiaqi Y, Hori S, Minamitani K et al (1996) A new embolic material: super absorbent polymer (SAP) microsphere and its embolic effects. Nippon Igaku Hoshasen Gakkai Zasshi 56(1):19–24
Osuga K, Hori S, Kitayoshi H et al (2002) Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres. J Vasc Interv Radiol 13(11):1125–1133
Osuga K, Khankan AA, Hori S et al (2002) Transarterial embolization for large hepatocellular carcinoma with use of superabsorbent polymer microspheres: initial experience. J Vasc Interv Radiol 13(9; Pt 1):929–934
Osuga K, Murakami T, Nakamura H, Hori S (2001) A new embolic material: SAP-microsphere. Nippon Rinsho 59(Suppl 6):534–538
Khankan AA, Osuga K, Hori S, Morii E, Murakami T, Nakamura H (2004) Embolic effects of superabsorbent polymer microspheres in rabbit renal model: comparison with tris-acryl gelatin microspheres and polyvinyl alcohol. Radiat Med 22(6):384–390
Acknowledgments
This work was supported by a grant from BioSphere Medical and by the Charles W. Pratt Fund for Liver Cancer Research (J.F.G. and K.H.L).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, KH., Liapi, E.A., Cornell, C. et al. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer. Cardiovasc Intervent Radiol 33, 576–582 (2010). https://doi.org/10.1007/s00270-010-9794-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00270-010-9794-1