TITLE:
Polymer Delivery of Hydroxycamptothecin against C6 Glioma
AUTHORS:
Jing Hu, Huafei Tang, Songqing Liu
KEYWORDS:
Hydroxycamptothecin Polylactic Acid (PLA) C6 Glioma Sustained Release
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.10,
September
4,
2014
ABSTRACT:
Hydroxycamptothecin is a
potent antineoplastic agent that has shown efficacy against multiple tumor
lines in vitro. This is
the first study to investigate the release, distribution, and efficacy of
hydroxycamptothecin which was incorporated into the biodegradable polymer
Polylactic Acid (PLA), and implant into brain directly. In vitro release curve generated showed that a
large initial release occurred over the first three days and was followed by a
steady, but considerably slower rate of release over the next 25 days. After
implanting the discs into 40 male SD rats, the animals were followed up to 28
days, where the concentration in brain tissue was far higher than that in
peripheral blood at the each of the eight time-points evaluated, and it was
also within the therapeutic range for C6 cells tested in vitro. The in vivoefficacy of the discs
was evaluated with rats inoculated intracranially with C6 glioma and treated
with hydroxycamptothecin polymer compared to intravenous as well as
intratumoral injections; the median survival is 21.1, 13.9, 14.9 days,
respectively. Given these data, we conclude that the biodegradable polymer PLA
releases hydroxycamptothecin, producing tumoricidal levels in brain tissues and
prolonging survival in a rat glioma model.