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KMID : 0043320150380101822
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Archives of Pharmacal Research
2015 Volume.38 No. 10 p.1822 ~ p.1829
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Comparative effects of PEG-containing liposomal formulations on in vivo pharmacokinetics of streptokinase
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Jin Su-Eon
Kim In-Sook
Kim Chong-Kook
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Abstract
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Streptokinase (SK) is an effective thrombolytic agent, but it has a short half-life due to its rapid elimination from the body. In this study, we prepared and evaluated polyethyleneglycol (PEG)-based liposomal formulations (PEG-liposomes) containing SK with a view toward prolonging its circulatory half-life. SK-bearing liposomes (SK-liposomes) were prepared using freeze?thaw method after film hydration and extrusion techniques, composed of phosphatidylcholine [egg phosphatidylcholine (EPC), dipalmitoyl PC, or distearoyl PC], cholesterol and cholesterol-3-sulfate with or without PEG. Their physicochemical properties were characterized by the measurement of size and zeta potential and incorporation efficiency. SK-liposomal formulations were applied to rats through a femoral vein via intravenous administration to compare the effects of liposomal delivery and PEG on the half-life of SK in blood. Free SK was used as a control. SK activities in plasma were measured to estimate the amidolytic activity of SK-plasminogen complex after rupturing liposomes with Triton X-100. Pharmacokinetic parameters were obtained from SK activity-time profiles. The SK-liposomes had a homogenous distribution of negatively charged nanoparticles at the range of 10?33 % of the incorporation efficiencies of SK. Among the SK-liposomes, SK-EPC- and SK-EPC/PEG-liposomes had injectable diameters (<200 nm). SK was administered as free SK, SK-EPC-liposomes, or SK-EPC/PEG-liposomes for in vivo study. SK-EPC/PEG-liposomes had significantly greater the t1/2, AUC∞ and MRT values of SK than SK alone or SK-EPC-liposomes. These findings suggest that PEG-liposomal incorporation of SK enhances thrombolytic activity in vivo, and that such liposomes can be utilized to enhance the pharmacokinetic profiles of other therapeutic proteins with a short biological half-life.
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KEYWORD
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Streptokinase, Long-circulating liposomes, Pharmacokinetics
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