Dual phosphatidylglyceroglycerol-based thermosensitive liposomes for MR-guided chemothermotherapy

Abstract

Phosphatidylglyceroglycerol (DPPGOG)-based thermosensitive liposomes (TSL) with either encapsulated proton (1H) magnetic resonance (MR) contrast agent gadodiamide (Gd-DTPA-BMA) or doxorubicin (DOX) have been proposed for noninvasive online temperature monitoring and drug release respectively during tumor treatment using chemotherapy combined with hyperthermia. The technique exploits the fact that water exchange between the TSL interior and exterior is increased and/or the encapsulated Gd-DTPA-BMA or DOX is released near the gel-to-liquid crystalline phase transition temperature of TSL, and thus shortens the 1H MR longitudinal relaxation time (T1) of tissue and increases drug delivery to tissue. In this work, DPPGOG-TSL with encapsulated Gd-DTPA-BMA were mixed with those with encapsulated DOX. The resulting suspension was characterized in vitro by measuring the temperature dependence of the T1 and DOX fluorescence intensity while temperature was increased from 30 and 46 °C. The measurements revealed that from 37 to 44°C, the T1 markedly decreased and DOX fluorescence intensity increased since encapsulated Gd-DTPA-BMA and DOX were simultaneously rapidly released. © 2009 Springer-Verlag.