The Study of Long-circulating Liposomes'therapeutic Efficacy in a Murine Lymphoma Model

• Main Authors: Liu, Shih-Hao, 劉士豪
• Other Authors: Chang Fu-Hsiung
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/51448593579685253882

碩士 === 國立臺灣大學 === 生化學研究所 === 85 === ABSTRACT The traditional anti-cancer drugs such as doxorubicin and vincristine can be used against a broad spectrum of cancers but have been associated with a number of significant side effects. Long-circulating liposomes have been demonstrated to prolong the circulation half-life of the anti-cancer drugs, and narrow down the drugs' biodistribution to specific disease sites. Because of these advantages, long-circulating liposomes can reduce the side effects and maintain or improve the therapeutic efficacy of the anti-cancer drugs. In this investigation, we used long-circulating liposomes to encapsulate a new anti-cancer drug, Navelbine. The in vitro cytotoxicity of Navelbine was superior than doxorubicin, a common used anti- cancer drug, when used against the 38c-13 tumor cells. By using a transmembrane ammonium sulfate gradient, Navelbine could undergo efficient and remote loading into the long- circulating liposomes. The loading efficiency was maintained at a high level (> 70 %) when the cholesterol content of the liposomes was higher than 20 mol %. In the study of pharmacokinetics, the long-circulating liposomes prolonged the drug's circulation half-life in C3H/HeN mice from 5 min to 124 min. Furthermore, the route of tumor implantation (intraperitoneal or intravenous) did not affect the in vivo therapeutic efficacy of liposomal Navelbine against the 38C-13 lymphoma. However, the therapeutic efficacy of liposomal Navelbine was higher when the tumor cells were implanted by intraperitoneal route. ( The life span was increased by 193 %). These results indicated that the long- circulating liposomes improved the Navelbine's therapeutic efficacy by prolonging its circulation half-life.