TEMPERATURE SENSITIVE LIPOSOMES FOR LOCAL DRUG DELIVERY USING MRI AND FU

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Hyperthermia and the liposomal drug delivery have been extensively evaluated in the past decade for drug delivery. Needham and collaborators [1-2] have developed different thermosensitive liposome formulations of which, one, ThermoDox¿, has been approved by the FDA for use in clinical trials. Since 2003, ongoing trials with ThermoDox in prostate cancer patients in association with radiofrequency ablation therapy have been encouraging. Similar formulations can be improved if molecularly targeted. MR imaging with thermo-mapping, and thermotherapy are powerful combinations for improved local treatment of disease. Specific Aims: Synthesis, characterization, and cancer efficacy studies of new molecularly targeted temperature sensitive liposomes using combined MRI and focused ultrasound techniques. Materials and Methods: We have developed an easy process to formulate thermosensitive liposomes (TSLs) for cancer therapy. As an initial model, bioluminesence imaging was used to monitor the release of luciferin from TSLs in response to increases in temperature. This model allows a quick and sensitive method for optimization of formulations. After optimization of the process, the size and the stability of the TSLs were studied in buffer and serum. Red blood cells were used to determine possible cell and membrane toxicity. Cell aggregation was also evaluated.