title: Comparative effects of PEG-containing liposomal formulations on in vivo pharmacokinetics of streptokinase.
abstract: 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 t(1/2), 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.
authors: College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
authors: Su-Eon
authors: SE
authors: Jin
authors: College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
authors: In-Sook
authors: IS
authors: Kim
authors: College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea. ckkim@snu.ac.kr.|College of Pharmacy, Inje University, Gimhae, Gyeongnam, 621-749, Republic of Korea. ckkim@snu.ac.kr.
authors: Chong-Kook
authors: CK
authors: Kim
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D008081:Liposomes; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010958:Plasminogen / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013300:Streptokinase / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D005343:Fibrinolytic Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D011092:Polyethylene Glycols; D010958:Plasminogen; D013300:Streptokinase
keywords: Long-circulating liposomes; Pharmacokinetics; Streptokinase