A serious limitation of conventional chemotherapy is the unspecific distribution of cytotoxic drugs within the body resulting in reduced therapeutic efficacy and systemic side effects. In contrast, cytotoxic drugs formulated as nanoparticulate or liposomal delivery systems favor accumulation in solid tumors due to abnormal tumor physiology. Several liposomal cytotoxic drugs are already commercially available like liposomal Doxorubicin (Caelyx®). However, there are still disadvantages associated with such liposome products and the therapeutic-to-toxicity ratio is still borderline.
During the last decade various approaches have been investigated to enhance targeted drug delivery via triggered release, e.g. by application of heat (hyperthermia), enzymatic and pH mediated strategies. Another promising means is to combine ultrasound with ultrasound responsive drug carriers. Focused and low frequency ultrasound is applied to the target (tumor) tissue resulting in both enhanced release of drug from the carrier and concomitant increased drug uptake into tumor tissue as well as tumor cells. Toxicity to healthy tissue may be avoided as a result of reduced doses and selectively exposing the tumor volume to ultrasound. A joint research program between companies Epitarget (Oslo, Norway), EDAP-Technomed (Vaulx-en-Velin) and LabTAU resulted in the development of an ultrasonic device for activating sono-sensitive drug-loaded liposomes. A first proof of concept in vivo was made in a prostatic tumor model which does not normally respond particularly well to doxorubicin.
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