Targeted delivery of active agents using thermally stimulated large increase of perfusion by high intensity focused ultrasound

Abstract

In some embodiments, the present disclosure pertains to a method of delivery of an active agent to a target tissue, in a subject in need thereof comprising positioning a high intensity focused ultrasound transducer to enable delivery of ultrasound energy to the target tissue. Such a method comprises energizing the high intensity focused ultrasound transducer; imaging at least a portion of the target tissue; and discontinuing delivery of ultrasound energy. Further, such a method may comprise administering the active agent to the subject under the conditions of thermal stimulation. In another embodiment, the present disclosure relates to a method of treating a tumor in a subject in need thereof comprising administering a therapeutic agent to the subject and providing thermal stimulation to the tumor. In some embodiments, there is provided a method for increasing the efficacy of a therapeutic agent in a target tissue.

What is claimed is: 
     
         1 . A method of delivery of an active agent to a target tissue, in a subject in need thereof, comprising the steps of:
 identifying the target tissue in the subject;   positioning a high intensity focused ultrasound transducer;   energizing the high intensity focused ultrasound transducer to thermally stimulate the target tissue;   imaging at least a portion of the target tissue that includes the volume of the target tissue being thermally stimulated; and   discontinuing delivery of ultrasound energy when said target tissue achieves a pre-determined set temperature or temperature profile;   administering the active agent to the subject, wherein the thermal stimulation causes a temperature dependent large increase of blood perfusion to the target tissue.   
     
     
         2 . The method of  claim 1 , wherein the step of identifying the target tissue is by Magnetic Resonance Imaging (MRI) or by ultrasound. 
     
     
         3 . The method of  claim 1 , wherein the step of positioning comprises placement of the high intensity focused ultrasound transducer to concentrate the ultrasound energy on the target tissue. 
     
     
         4 . The method of  claim 3 , wherein the step of positioning the high intensity focused ultrasound transducer is by placing it within a vascular structure or an internal body cavity of the subject. 
     
     
         5 . The method of  claim 1 , wherein the step of energizing the high intensity focused ultrasound transducer comprises applying a frequency of ultrasound ranging from about 0.8 MHz and about 4.0 MHz. 
     
     
         6 . The method of  claim 1 , wherein the step of imaging at least a portion of the target tissue is by magnetic resonance imaging. 
     
     
         7 . The method of  claim 1 , wherein the step of imaging is by ultrasound. 
     
     
         8 . The method of  claim 6 , wherein the imaging measures the temperature profile within the target tissue of the subject. 
     
     
         9 . The method of  claim 8 , wherein the temperature profile within the target tissue ranges from about 39° C. to about 99° C. 
     
     
         10 . The method of  claim 8 , wherein the temperature profile aids in controlling delivery of the high intensity focused ultrasound to the target tissue. 
     
     
         11 . The method of  claim 1 , wherein the active agent is administered simultaneously with the step of energizing the high intensity focused ultrasound transducer. 
     
     
         12 . The method of  claim 1 , wherein the active agent is administered before the step of energizing the high intensity focused ultrasound transducer. 
     
     
         13 . The method of  claim 1 , wherein the active agent is administered after the step of energizing the high intensity focused ultrasound transducer. 
     
     
         14 . The method of  claim 1 , wherein the active agent is designed to be heat activated. 
     
     
         15 . The method of  claim 1 , wherein the active agent is designed to be activated by mechanical vibrations. 
     
     
         16 . The method of  claim 1 , wherein the active agent further comprises a targeting moiety on its surface. 
     
     
         17 . The method of  claim 1 , wherein the active agent is contained within a particle. 
     
     
         18 . The method of  claim 17 , wherein the particle further comprises a targeting moiety on its surface. 
     
     
         19 . The method of  claim 1 , wherein the active agent is administered intravascularly. 
     
     
         20 . The method of  claim 1 , wherein the active agent is a diagnostic agent. 
     
     
         21 . The method of  claim 20 , wherein the diagnostic agent is an imaging agent. 
     
     
         22 . The method of  claim 1 , wherein the active agent is a therapeutic agent. 
     
     
         23 . The method of  claim 22 , wherein the therapeutic agent is also an imaging agent. 
     
     
         24 . The method of  claim 22 , wherein the therapeutic agent is activated by heat. 
     
     
         25 . The method of  claim 22 , wherein the therapeutic agent is activated by mechanical vibrations. 
     
     
         26 . The method of  claim 1 , wherein the target tissue is a pathological tissue. 
     
     
         27 . The method of  claim 1 , wherein the target tissue is a solid tumor selected from the group consisting of prostate carcinoma, breast carcinoma, hepatocellular carcinoma, renal cell carcinoma, urinary bladder carcinoma, pancreas cancer, and osteosarcoma. 
     
     
         28 . The method of  claim 1 , wherein the target tissue is uterine fibroid, fibroadenoma, or a hypertrophic prostatic tissue.