Temperature-triggered drug release formulations overcome limitations associated with the reported heterogeneous accumulation of nanomedicines within tumor tissue. This is achieved by quickly and efficiently releasing the drug cargo within the tumor vasculature. Hyperthermia treatment (e.g. high intensity focused ultrasound or laser application) is externally applied in order to selectively increase tumor temperatures several degrees above physiological conditions prior to intravenous administration of drug-loaded thermosensitive delivery vehicles. Upon reaching the warmed tumor vasculature, the drug is released and extravasates into the tumor interstitium.
At the Allen lab, we are utilizing thermosensitive liposomes with a bilayer transition temperature in the range of mild hyperthermia (39-45°C). Using this approach, we have successfully loaded a variety of chemotherapeutic compounds (i.e. doxorubicin, cisplatin, vinorelbine and alvespimycin) into thermosensitive liposome formulations. The delivery of drugs by this method is generally more efficient compared to free drug or traditional, non-thermosensitive formulations. The degree of diffusion of small chemotherapeutic molecules following heat-triggered release (into the tumor interstitium) has been shown to surpass that of larger nanomedicines. In addition, using site-specific drug release reduces the exposure of normal tissues relative to the administration of a free drug. This allows for increased dosing and/or provides a critical reduction in side effects.