Focused ultrasound can be used to release encapsulated drugs (e.g. genes, chemotherapeutics), delivering them in high concentrations to a precise point while minimizing their systemic effects.

In this process, a drug is encapsulated in or bonded to a carrier vehicle (e.g. microbubble, liposome), that is sensitive to either elevated temperatures or pressures1. These carrier vehicles are then injected into the bloodstream. This encapsulation prevents the drug from interacting with its surroundings as it circulates throughout the body. Next, ultrasound is focused on the targeted area, causing the carriers to release the drug or to decouple from the drug which is then quickly absorbed by the surrounding tissue. Although the encapsulated drug is present throughout the entire body, it is only released in the area targeted by focused ultrasound. In this way, the drug can circulate harmlessly throughout the body, and only be activated where desired.2-5

FUF-DrugDeliveryVehicles-FINAL

A significant amount of recent scientific work has been devoted to optimizing the various types of carrier vehicles such as microbubbles, liposomes, and nanoparticles. Release of drugs from microbubbles (i.e. ultrasound contrast agents) can be readily monitored in real time using ultrasound imaging. If drugs are coupled to MRI contrast agents, MRI can also be used for monitoring. With the use of low temperature sensitive liposomes (LTSLs), high intensity focused ultrasound is used to induce mild hyperthermia in a targeted location, characterized by a temperature elevation to approximately 40ºC3,6. As LTSLs pass through the hyperthermic region, the increased temperature causes their decomposition and the subsequent release of encapsulated drugs3,5. For acoustic pressure-sensitive carriers, ultrasound induced cavitation and radiation forces can “pop open” the carrier or decouple the drugs from the carriers, allowing for their release in the targeted area7.

Hyperthermia6, stable cavitation8, and radiation forces9 from focused ultrasound have all been shown to increase local drug absorption from the bloodstream. In heated tissue, blood flow and the rate of chemical diffusion are both enhanced6, leading to more efficient uptake of drugs into the surrounding tissue. Stable cavitation induces acoustic streaming and increases cell membrane permeability8, which also locally increases drug bioavailability.

Clinically, combining focused ultrasound with drug delivery vehicles presents an attractive method for chemotherapy delivery. These drugs, which are typically delivered systemically, are very toxic to healthy cells. By taking advantage of drug delivery vehicles, chemotherapeutics can be delivered at high concentrations in the tumor without the systemic toxicities. These vehicles can also be used to deliver genes to specific targets in the brain to treat neurological disorders.

References:

[1] Couture O, Foley J, Kassell NF, Larrat B, Aubry J-F. Review of ultrasound mediated drug delivery for cancer treatment: updates from preclinical studies. Transl. Cancer Res. 2014;3:494–511.

[2] M. Thanou and W. Gedroyc, “MRI-Guided Focused Ultrasound as a New Method of Drug Delivery.,” J. drug Deliv., vol. 2013, May 2013. 

[3] H. Grüll and S. Langereis, “Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound.,” J. Control. Release : Off. J. Control. Release Soc., vol. 161, no. 2, pp. 317–327, Jul. 2012. 

[4] S. Ibsen, M. Benchimol, D. Simberg, and S. Esener, “Ultrasound mediated localized drug delivery.,” Adv. Exp. Med. Biol., vol. 733, pp. 145–153, 2012. 

[5] Y. Zhou, “Ultrasound-mediated drug/gene delivery in solid tumor treatment.,” J. Healthc. Eng., vol. 4, no. 2, pp. 223–254, 2013. 

[6] May JP, Li S-D. Hyperthermia-induced drug targeting. Expert Opin. Drug Deliv. 2013;10:511–27.

[7] C. Oerlemans, R. Deckers, G. Storm, W. E. Hennink, and J. F. W. Nijsen, “Evidence for a new mechanism behind HIFU-triggered release from liposomes.,” J. Control. Release : Off. J. Control. Release Soc., vol. 168, no. 3, pp. 327–333, Jun. 2013.

[8] Liang H-D, Tang J, Halliwell M. Sonoporation, drug delivery, and gene therapy. Proc. Inst. Mech. Eng. [H]. 2010;224:343–61.

[9] Uchida T, Nakano M, Hongo S, Shoji S, Nagata Y, Satoh T, et al. High-intensity focused ultrasound therapy for prostate cancer. Int. J. Urol. Off. J. Jpn. Urol. Assoc. 2012;19:187–201.

Click here for additional references from PubMed.

 
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