Liposomal anthracyclines offer considerable improvements in toxicity and preferential tumor accumulation, however, stable drug entrapment limits their therapeutic benefit due to reduced drug bioavailability. A strategy to improve that is to combine temperature-sensitive liposomes (TSL) with hyperthermia (HT) to spatiotemporally trigger selective drug release. To study the pharmacokinetics of various types of clinically relevant TSL, three different liposome systems were dual-labeled with 3H-CHE lipid and loaded with 14C-doxorubicin. Their blood profile, tissue distribution and therapeutic efficacy were studied to determine the localization of liposome and doxorubicin tumor-accumulation on therapeutic efficacy. The TSL system with lowest serum stability, showed rapid drug release kinetics and the highest doxorubicin release (7.6%ID/g) 1h after HT. Alternatively, serum-stable systems showed impressive tumor accumulation from 15 to 30%ID/g 24hr post-HT, however, did not lead to improved therapeutic efficacy. Overall our results emphasize the importance of matching the HT protocol with the thermoresponsive and pharmacokinetic characteristics of the liposomal doxorubicin to maximize therapeutic benefit.

Thermosensitive liposomal doxorubicin and tumor hyperthermia: Matching the heating protocol with the liposome system

243rd National Meeting (2012)

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