In vitro evaluation of the association of thermosensitive liposome-encapsulated doxorubicin with hyperthermia.

Doxorubicin was encapsulated in small unilamellar thermosensitive liposomes which were strictly defined in terms of size distribution and size stability: more than 95% of vesicles with a maximal diameter of 50 nm stable for a minimum of 24 hours. In addition, the preparation procedure was optimised to achieve the highest differential thermal stability defined as the difference of release between 37 degrees and 43 degrees C exposures in serum-containing medium (dipalmitoylphosphatidylocholine/distearoylphosphatidylcholine/cho lesterol mixture in 5:4:2 molar ratio). The cytotoxicity of thermosensitive-liposome encapsulated doxorubicin was then evaluated in combination with 43 degrees C hyperthermia on HelaS3 human tumour cells using colony-forming assays. Results confirmed that hyperthermia potentiates the cytotoxic effects of doxorubicin. Liposome encapsulation was found to further enhance these effects when 0.05 mumol/l doxorubicin concentration was used.