Abstract

The delivery of cancer drugs such as topotecan and doxorubicin poses risks such as off target tissue interactions and systemic toxicity. The use of thermosensitive liposomes provides a targeted manner to deliver such drugs with minimal risk, since drug release occurs upon administration of hyperthermia at the target site, such as focused ultrasound. Topotecan and doxorubicin were tested for their suitability in the design of a thermosensitive liposome formulation, using the film hydration method to produce thermosensitive liposomes. The lipid film was hydrated with ammonium sulphate buffer (300 mM pH 4.0), with subsequent gas extrusion. The exterior of the liposomes was adjusted to pH 7.4 with buffer followed by drug loading by incubation at 38°C. Differential scanning calorimetry, dynamic light scattering, and fluorescence measurements were carried out as characteristic tests. Thermosensitive liposomes with a TM of 46°C and an approximate diameter of 100nm were produced, while releasing their drug payload between 39°C-42°C. Doxorubicin ’ s self-quenching properties prevented accurate release profile fluorescence readings. Therefore, topotecan is a better suited model drug for the design and optimization of a thermosensitive liposome formulation compared to doxorubicin, reducing the risk of drug leakage outside of target site. Thermosensitive liposomes were successfully formulated with topotecan and doxorubicin.

Keywords: Thermosensitive liposomes; High intensity focused ultrasound; Targeted drug delivery