Drug Delivery with Temperature Sensitive Liposomes

The drawbacks of standard chemotherapy treatments are well known, and are due primarily to the interaction of the drug with bodily systems outside of the targeted cancerous region. More recent treatments using liposomes as delivery vehicles for chemotherapeutic drugs have shown promise in reducing cardiotoxic side effects of the encapsulated drug doxorubicin. However, for delivery of the drug these formulations rely on slow leakage of the drug from within the liposome, which is indiscriminate and may impact healthy tissue as well as the targeted cancer. By using liposomes which release their contents at a prescribed temperature, drug delivery could be more controlled and improved.  Different encapsulation schemes were investigated to determine which yielded the highest encapsulation of doxorubicin. Concentrations of the drug were measured using fluorescence spectroscopy, and the changes in fluorescence intensity before and after lysis was related to the amount of encapsulate.  For controlled release, gold nanoshells were tethered to the liposomes and irradiated by laser to heat the membrane to its release temperature. Results show that optimal encapsulation is achieved using an ammonium sulfate ion gradient across the membrane at temperatures just below the release temperature, and loaded for approx. 16.5 hours. Preliminary results show that irradiation of the gold nanoshells leads to localized heating and drug release from the liposomes. These results suggest that this may be a viable strategy for controlled drug delivery to tumors.