| Summary: | 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.
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