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The use of PEGylated liposomes to prolong circulation lifetimes of tissue plasminogen activator

Title
The use of PEGylated liposomes to prolong circulation lifetimes of tissue plasminogen activator
Author
김진기
Keywords
Tissue plasminogen activator; Half-life; Prolong; Liposomes; PEG; Fibrinolysis
Issue Date
2009-10
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v. 30, No. 29, Page. 5751-5756
Abstract
Tissue plasminogen activator (tPA), a widely used thrombolytic agent, has an application limit due to short half-life. To prolong the half-life of tPA, liposomes composed of egg phosphatidylcholine (EPC), cholesterol (CHOL) and sodium cholesterol-3-sulfate (CS) were prepared by lipid film method. In addition, distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) 2000 (DSPE-PEG 2000) was included to give steric barrier to liposomes. Physicochemical characteristics such as particle size, zeta potential, entrapment efficiency and long-term storage stability at 4 degrees C were investigated. The fibrinolytic activity of tPA-loaded in liposomes was confirmed by fibrin clot lysis assay. In vivo pharmacokinetic properties of tPA and the effect of PEG on the blood circulation of tPA-loaded in liposomes in circulation were also evaluated. Both conventional liposomes (EPCL) and PEGylated liposomes (EPC-PEGL) were proper as an injectable formulation with small particle size. Loading process of tPA into liposomes did not alter fibrinolytic activity of intact tPA. Encapsulation of tPA into EPCL and EPC-PEGL prolonged half-life of tPA by 16 and 21 folds compared with free tPA, respectively. Therefore, the use of liposomes could prolong the circulation lifetimes and longevity effect of liposomes on tPA was increased by PEG. (C) 2009 Elsevier Ltd. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S014296120900725X?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/76478
ISSN
0142-9612
DOI
10.1016/j.biomaterials.2009.07.021
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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