Abstract
Purpose. We applied non-invasive and real-time method with in vivo ESR spectroscopy to determining pharmacokinetics and metabolism of lipid emulsion as a drug carrier in living mice.
Methods. A spin-labeled triglyceride (SL-TG) was newly synthesized and lipid emulsion containing SL-TG was prepared. In vivo ESR spectra in mice were observed after intravenous administration of the lipid emulsion.
Results. In vivo ESR spectra consisted of three components, coinciding with the in vitro spectra of SL-TG particles, free and immobilized fatty acids. The amount of the components depended on both the observing domain and the period after administration. In the chest, all three components were observed, while SL-TG particle was lacking in the abdomen. The half-life of the lipid particles in the chest was 2 hr.
Conclusions. Non-invasive and real-time analysis of drug carriers in living animal is successfully accomplished using an in vivo ESR method.
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REFERENCES
Y. Mizushima and K. Hoshi. Recent advances in lipid microsphere technology for targeting prostaglandin delivery. J. Drug Targeting 1:93–100 (1993).
T. Yamaguchi, Y. Fukushima, S. Itai, and H. Hayashi. Rate of release and retentivity of prostaglandin E1 in lipid emulsion. Biochim. Biophys. Acta. 1256:381–386 (1995).
S. Otomo, Y. Mizushima, H. Aihara, K. Yokoyama, M. Watanabe, and A. Yanagawa. Prostaglandin E1 incorporated in lipid microspheres (lipo PGE1). Drug Exp. Clin. Res. 11:627–631 (1985).
L. Illum, P. West, C. Washington, and S. S. Davis. The effect of stabilising agents on the organ distribution of lipid emulsions. Int. J. Pharm. 54:41–49 (1989).
T. Yoshioka, J. Noma, K. Eguchi, and K. Sekiba. Lipid metabolism in pregnancy, metabolism of intravenously injected fat emulsion. Acta. Obst. Gynaec. Japan. 33:34–40 (1981).
H. Utsumi, K. Takeshita, Y. Miura, S. Masuda, and A. Hamada. In vivo ESR measurement of radical reaction in whole mice.—Influence of inspired oxygen and ischemia-reperfusion injury on nitroxide reduction—Free Rad. Res. Commus. 19:s219–225 (1993).
Y. Miura, A. Hamada, and H. Utsumi. In vivo ESR studies of antioxidant activity on free radical reaction in living mice under oxidative stress. Free Rad. Res. 22:209–214 (1995).
F. Gomi, H. Utsumi, A. Hamada, and M. Matsuo. Aging retards spin clearance from mouse brain and food restriction prevents its age-dependent retardation. Life Science 52:2027–2033 (1993).
K. Takeshita, H. Utsumi, and A. Hamada. ESR measurement of radical clearance in lung of whole mouce. Biochem. Biophys. Res. Commun. 177:874–880 (1991).
A. S. Waggoner, T. J. Fingzett, S. Rotschaeter, O. H. Griffith, and A. D. Keith. A spin-labeled lipid for probing biological membrances. Chem. Phys. Lipids. 3:245–253 (1969).
T. Yamaguchi, K. Nishizaki, S. Itai, H. Hayashi, and H. Ohshima. Physicochemical characterization of parenteral lipid emulsion: Influence of cosurfactants on flocculation and coalescence. Pharm. Res. 12:1273–1278 (1995).
H. Utsumi, K. Inoue, S. Nojima, and T. Kwan. Interaction of spin-labeled lysophosphatidylcholine with rabbit erythrocytes. Biochemistry 17:1990–1998 (1978).
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Yamaguchi, T., Itai, S., Hayashi, H. et al. In Vivo ESR Studies on Pharmacokinetics and Metabolism of Parenteral Lipid Emulsion in Living Mice. Pharm Res 13, 729–733 (1996). https://doi.org/10.1023/A:1016047532687
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DOI: https://doi.org/10.1023/A:1016047532687