ABSTRACT
Purpose
The need for computed tomography (CT) of reticuloendothelial system (RES)-rich organs such as the liver is increasing, particularly in patients with suspected hepatic metastasis. CT images of the liver have been improved by encapsulating currently used, water-soluble iodine contrast agent in liposomes. The present study was performed to investigate a possibility to overcome the limitations of entrapped iodine in liposomes by preparing liposomes co-loaded with iopamidol, a water-soluble iodinated compound, and lipiodol, an iodized oil.
Methods
Iopamidol and lipiodol were simultaneously loaded in liposomes by modified reverse-phase evaporation method. The entrapped iodine concentration, mean particle size and polydispersity index of resulting liposomes were evaluated. Following intravenous injection of these liposomes into rats, CT scanning was performed.
Results
Simultaneous loading of iopamidol and lipiodol into liposomes resulted in entrapped iodine concentrations as high as 49.2 iodine mg/ml. The mean particle size was 280 nm, and the mean polydispersity index was 0.230. CT scanning with these iopamidol/lipiodol (I/L) liposomes into rats resulted in more pronounced and more persistent increases in RES-rich organs, liver and spleen, compared with free liposomes or liposomes loaded with iopamidol alone.
Conclusions
These findings indicate that I/L liposomes have the potential to allow thorough CT examination of RES-rich organs.
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REFERENCES
Krauze MT, Forsayeth J, Park JW, Bankiewicz KS. Real-time imaging and quantification of brain delivery of liposomes. Pharm Res. 2006;23:2493–504.
Garbino J, Adam A. Use of high-dose liposomal amphotericin B: efficacy and tolerance. Acta Biomed. 2006;19(22):19–22.
Rutten A, Prokop M. Contrast agents in X-ray computed tomography and its applications in oncology. Anticancer Agents Med Chem. 2007;7:307–16.
Jang HJ, Yu H, Kim TK. Imaging of focal liver lesions. Semin Roentgenol. 2009;44:266–82.
Ryan PJ, Davis MA, DeGaeta LR, Woda B, Melchior DL. Liposomes loaded with contrast material for image enhancement in computed tomography. Work in progress. Radiology 1984;152:759–62.
Seltzer SE, Blau M, Herman LW, Hooshmand RL, Herman LA, Adams DF et al. Contrast material-carrying liposomes: biodistribution, clearance, and imaging characteristics. Radiology 1995;194:775–81.
Krause W, Leike J, Sachse A, Schuhmann-Giampieri G. Characterization of iopromide liposomes. Invest Radiol. 1993;28:1028–32.
Petersein J, Franke B, Fouillet X, Hamm B. Evaluation of liposomal contrast agents for liver CT in healthy rabbits. Invest Radiol. 1999;34:401–9.
Mukundan Jr S, Ghaghada KB, Badea CT, Kao CY, Hedlund LW, Provenzale JM et al. A liposomal nanoscale contrast agent for preclinical CT in mice. AJR Am J Roentgenol. 2006;186:300–7.
Kim JT, Heo SH, Choi SM, Lee SH, Park MS, Kim BC et al. Cerebral embolism of iodized oil (lipiodol) after transcatheter arterial chemoembolization for hepatocellular carcinoma. J Neuroimaging. 2009;19:394–7.
Kohnoe S, Takahashi I, Kawanaka H, Mori M, Okadome K, Sugimachi K. Combination of preoperative lymphangiography using lipiodol and intraoperative lymphangiography using Evans Blue facilitates the accurate identification of postoperative chylous fistulas. Surg Today. 1993;23:929–31.
Nacka F, Cansell M, Meleard P, Combe N. Incorporation of alpha-tocopherol in marine lipid-based liposomes: in vitro and in vivo studies. Lipids 2001;36:1313–20.
Szoka Jr F, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA. 1978;75:4194–8.
Lim SJ, Kim CK. Formulation parameters determining the physicochemical characteristics of solid lipid nanoparticles loaded with all-trans retinoic acid. Int J Pharm. 2002;243:135–46.
Stewart JLM. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem. 1959;104:10–4.
Allen TM, McAllister L, Mausolf S, Gyorffy E. Liposome-cell interactions. A study of the interactions of liposomes containing entrapped anti-cancer drugs with the EMT6, S49 and AE1 (transport-deficient) cell lines. Biochim Biophys Acta. 1981;643:346–62.
Desser TS, Rubin DL, Muller H, McIntire GL, Bacon ER, Toner JL. Blood pool and liver enhancement in CT with liposomal lodixanol: comparison with lohexol. Acad Radiol. 1999;6:176–83.
Sachse A, Leike JU, Rossling GL, Wagner SE, Krause W. Preparation and evaluation of lyophilized iopromide-carrying liposomes for liver tumor detection. Invest Radiol. 1993;28:838–44.
Leike J, Sachse A, Ehritt C. Biodistribution and CT-imaging characteristics of iopromide-carrying liposomes in rats. J Liposome Res. 1996;6:665–80.
Seltzer SE, Davis MA, Adams DF, Shulkin PM, Landis WJ, Havron A. Liposomes carrying diatrizoate. Characterization of biophysical properties and imaging applications. Invest Radiol. 1984;19:142–51.
Sharma SK. Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent? J Invasive Cardiol. 2008;20:245–8.
Sachse A, Leike JU, Schneider T, Wagner SE, Rossling GL, Krause W et al. Biodistribution and computed tomography blood-pool imaging properties of polyethylene glycol-coated iopromide-carrying liposomes. Invest Radiol. 1997;32:44–50.
Kong WH, Lee WJ, Cui ZY, Bae KH, Park TG, Kim JH et al. Nanoparticulate carrier containing water-insoluble iodinated oil as a multifunctional contrast agent for computed tomography imaging. Biomaterials 2007;28:5555–61.
Bourin M, Jolliet P, Ballereau F. An overview of the clinical pharmacokinetics of x-ray contrast media. Clin Pharmacokinet. 1997;32:180–93.
Solomon RJ, Mehran R, Natarajan MK, Doucet S, Katholi RE, Staniloae CS et al. Contrast-induced nephropathy and long-term adverse events: cause and effect? Clin J Am Soc Nephrol. 2009;4:1162–9.
ACKNOWLEDGEMENT
This study was supported by a faculty research grant of Yonsei University College of Medicine (6-2008-225) to J.S. Lim.
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Kweon, S., Lee, HJ., Hyung, W.J. et al. Liposomes Coloaded with Iopamidol/Lipiodol as a RES-Targeted Contrast Agent for Computed Tomography Imaging. Pharm Res 27, 1408–1415 (2010). https://doi.org/10.1007/s11095-010-0135-5
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DOI: https://doi.org/10.1007/s11095-010-0135-5