Ultrasound triggered, image guided, local drug delivery

Ultrasound allows the deposition of thermal and mechanical energies deep inside the human body in a non-invasive way. Ultrasound can be focused within a region with a diameter of about 1 mm. The bio-effects of ultrasound can lead to local tissue heating, cavitation, and radiation force, which can be used for 1) local drug release from nanocarriers circulating in the blood, 2) increased extravasation of drugs and/or carriers, and 3) enhanced diffusivity of drugs. When using nanocarriers sensitive to mechanical forces (the oscillating ultrasound pressure waves) and/or sensitive to temperature, the content of the nanocarriers can be released locally. Thermo-sensitive liposomes have been suggested for local drug release in combination with local hyperthermia more than 25 years ago. Microbubbles may be designed specifically to enhance cavitation effects. Real-time imaging methods, such as magnetic resonance, optical and ultrasound imaging have led to novel insights and methods for ultrasound triggered drug delivery. Image guidance of ultrasound can be used for: 1) target identification and characterization; 2) spatio-temporal guidance of actions to release or activate the drugs and/or permeabilize membranes; 3) evaluation of bio-distribution, pharmacokinetics and pharmacodynamics; and 4) physiological read-outs to evaluate the therapeutic efficacy.

Graphical abstractAnalysis of the temporal window for US-mediated internalization using Sytox green as a model drug since its fluorescence is increased several fold as it intercalates with DNA.Figure optionsDownload full-size imageDownload high-quality image (118 K)Download as PowerPoint slide