Ultrasound-enhanced tumor targeting of polymeric micellar drug carriers.

Cancer chemotherapy is often complicated by toxic side effects of anticancer drugs. We are developing a new modality of tumor chemotherapy aimed at circumventing side effects of treatment via drug targeting to tumors. The technique is based on drug encapsulation in polymeric micelles followed by a controlled drug release at a target site triggered by ultrasonic irradiation. The encouraging in vitro results of previous years warranted animal experiments for verification of the in vivo feasibility of the proposed technique. We report here on the effect of ultrasound on a biodistribution of a micellar drug carrier (fluorescently labeled Pluronic micelles) in ovarian cancer-bearing nu/nu mice. The degree of carrier accumulation in the cells of various organs was characterized by flow cytometry. Polymeric micelles were formed in either pure Pluronic P-105 solutions (unstabilized micelles) or 1:1 (weight) mixtures of Pluronic P-105 with PEG-diacylphospholipid (stabilized micelles). Intraperitoneal (ip) and intravenous (iv) injections were compared. The data showed that a 30 s ultrasonic irradiation by 1 or 3 MHz ultrasound applied locally to the tumor significantly enhanced accumulation of Pluronic in the tumor cells, which was observed for both ip and iv injections and for unstabilized and stabilized micelles. The data indicated targeting of Pluronic micelles to the tumors; the degree of targeting was enhanced by a local tumor sonication.