Stable nanoemulsions for ultrasound-mediated drug delivery and imaging
Described herein are nanoemulsions comprising (1) at least one fluoro ether and (2) a block copolymer comprising a hydrophilic block and hydrophobic block, wherein the nanoemulsion comprises a therapeutic agent in the nanoemulsion. The nanoemulsions are stable and are excellent drug delivery devices for ultrasound-mediated, image guided drug delivery. Also described herein are methods for using the nanoemulsions to treat tumors and cancers as well as using them as imaging agents.
1. A nanoemulsion comprising (1) at least one perfluoro crown ether and (2) polyethylene glycol poly(d,l)lactic acid block copolymer, wherein the nanoemulsion comprises a therapeutic agent encapsulated in the nanoemulsion.
2. The nanoemulsion of claim 1 , wherein the perfluoro crown ether is perfluoro 12-crown-4 ether, perfluoro 15-crown-5 ether, perfluoro 18-crown-6 ether, perfluoro 20-crown-7 ether, perfluoro dibenzo-18-crown-6 ether, perfluoro diaza-18-crown-6 ether, or any combination thereof.
3. The nanoemulsion of claim 1 , wherein the perfluoro crown ether is perfluoro 15-crown-5 ether.
4. The nanoemulsion of claim 1 , wherein the therapeutic agent comprises a chemotherapeutic drug.
5. The nanoemulsion of claim 1 , wherein the therapeutic agent comprises paclitaxel, doxorubicin, gemcitabine, adriamycin, cisplatin, taxol, methotrexate, 5-fluorouracil, betulinic acid, amphotericin B, diazepam, nystatin, propofol, testosterone, estrogen, prednisolone, prednisone, 2,3 mercaptopropanol, progesterone, or any combination thereof.
6. The nanoemulsion of claim 1 , wherein the therapeutic agent comprises paclitaxel, doxorubicin, or any combination thereof.
7. The nanoemulsion of claim 1 , further comprising at least one polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer.
8. A pharmaceutical composition comprising the nanoemulsion of claim 1 and a pharmaceutically acceptable carrier.
9. A method for treating a tumor comprising the steps:
(a) contacting the tumor with the nanoemulsion of claim 1 , wherein the therapeutic agent comprises a chemotherapeutic agent; and
(b) exposing the tumor to ultrasonic radiation.
10. The method of claim 9 , wherein the ultrasonic radiation comprises from about 30 kHz to about 20 MHz.
11. The method of claim 9 , wherein the tumor is a multidrug resistant tumor.
12. The method of claim 9 , wherein the tumor is breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, or colon cancer.
13. The method of claim 9 , further comprising imaging the tumor by 19 F MRI.
14. A method of treating a cancer in a subject comprising
i. administering the nanoemulsion of claim 1 to the subject, wherein the therapeutic agent comprises a chemotherapeutic agent; and
ii. exposing a tumor present in the subject to ultrasonic radiation.
15. The method of claim 14 , wherein the nanoemulsion is administered systemically to the subject by injection.
16. The method of claim 14 , further comprising imaging the tumor imaged by 19 F MRI.
17. A method for treating a tumor comprising the steps:
i. contacting the tumor with the nanoemulsion of claim 1 , wherein the therapeutic agent comprises a chemotherapeutic agent;
ii. imaging the tumor by 19 F MRI to identify the location of the nanoemulsion in the tumor; and
iii. exposing the tumor to ultrasonic radiation.
18. The method of claim 17 , wherein in step (b) the tumor is further imaged by 1 H MRI.
19. The method of claim 17 , wherein the ultrasonic radiation is unfocused ultrasound or focused ultrasound (FUS).
20. A method for delivering a therapeutic agent to the nucleus of a tumor cell comprising the steps:
i. contacting the tumor cell with the nanoemulsion of claim 1 ; and
ii. exposing the tumor cell to ultrasonic radiation.