1 research outputs found
Therapeutic Efficacy of Cisplatin Thermosensitive Liposomes upon Mild Hyperthermia in C26 Tumor Bearing BALB/c Mice
This study reports on the activity
of thermosensitive liposomes (TSLs) incorporating different HSPC ratios
in DPPC/MSPC/PEG<sub>2000</sub>-DSPE matrix (90/10/4) plus mild hyperthermia
(HT) (42 °C). TSLs were loaded with a poorly membrane permeable
anticancer drug, cisplatin, through the passive equilibration method.
The addition of HSPC to the corresponding DPPC lipid matrix increased
the transition temperature. <i>In vitro</i> data demonstrated
>90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within
10 min at 42 °C, while other TSLs bearing HSPC showed greater
stability. The plasma kinetics of cisplatin demonstrated higher cisplatin
leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL)
compared to other formulations. Indeed, increasing HSPC fraction in
liposome bilayers significantly improved drug retention in blood.
Though DPPC 90-LTSL plus one-step HT was expected to provide a unique
drug release, the premature drug leakage as well as the likely wash-back
of a great portion of drug into the blood circulation resulted in
reduced survival. On the other hand, stabilized DPPC 30/HSPC 60/MSPC
10/PEG<sub>2000</sub>-DSPE 4 liposomes plus two-step HT greatly enhanced
the survival of animals. In particular, the improved delivery of cisplatin
through stabilized DPPC 30/HSPC 60/MSPC 10/PEG<sub>2000</sub>-DSPE
4 liposomes in two-step mild HT enhanced antitumor efficacy compared
to other formulations. Thus, prolonged exposure of cancer cells to
cisplatin through stabilized liposomes would be an efficient approach
in improving the survival of animals