In vitro and in vivo activity of thermosensitive liposomes loaded with doxorubicin and cisplatin.

ABSTRACT

Thermosensitive liposomes loaded with cisplatin and doxorubicin composed of DPPC, DSPC, and DPPE-PEG5000 with different ratios were prepared by thin film hydration method. The Differential Scanning Calorimetry (DSC) curves showed that the liposomes composed of DPPC-DSPC-DPPE-PEG5000 with phospholipid ratio 9550.05 w/w were a suitable formulation as thermosensitive liposomes with a DSC peak at 42.1 °C. The effect of doxorubicin and cisplatin encapsulated non-thermosensitive and thermosensitive liposomes on cellular proliferation and IC50 in SKBR3 & MDA-MB-231 breast cancer and PC-3 & LNcaP prostate cancer cell lines was investigated. The results showed that doxorubicin loaded into thermosensitive liposomes showed 20-fold decrease in the IC50 at 42 °C while comparing it with the same at 37 °C. Also, the results showed a more than 35-fold and 12-fold decrease in the IC50 of cisplatin thermosensitive liposomes at 42 °C, while compared with free cisplatin and cisplatin thermosensitive liposomes at any temperature. The in vivo results showed that the effect of doxorubicin encapsulated thermosensitive liposomes at hyperthermic conditions during the treatment as the tumor growth inhibition was measured 1.5-fold higher than any of the liposomal formulations of doxorubicin. It was also noticed that the tumor volume reduced to 150 mm3 in doxorubicin thermosensitive liposomes (G8) after 3 weeks during the treatment, but increased to 196 mm3 after 4 weeks. The Kaplan-Meir curve showed the 100% survival of the animals from G8 (thermosensitive liposomes containing doxorubicin plus hyperthermia) after 12 weeks. The flow cytometry data revealed more than 25% apoptotic cells and 6.25% necrotic cells in the tumor cells from the tissues of the G8 group of the animals. The results clearly indicate the superior efficacy of doxorubicin and cisplatin containing thermosensitive liposomes treatment during hyperthermia.