Abstract
Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery.
Highlights
Therapeutic high intensity focused ultrasound (HIFU) or Focused Ultrasound (FUS) is a noninvasive medical treatment that allows the deposition of energy inside the human body
In our group we have investigated the potential of an MRI labelled phospholipid/lysolipid containing liposome to accumulate in tumours and release the drug under conditions of mild hyperthermia induced by FUS
The results demonstrated that Ktrans in the blood brain barrier (BBB)-opened region was at least two orders of magnitude higher when compared to the contralateral side [68]
Summary
Therapeutic high intensity focused ultrasound (HIFU) or Focused Ultrasound (FUS) is a noninvasive medical treatment that allows the deposition of energy inside the human body. In the 1950s Fry brothers developed a clinical FUS device for treating patients with Parkinson disease They used a sonication system in combination with X-rays to determine the target location relative to skull and to focus the ultrasound beam through a craniotomy into deep brain for effective functional neurosurgery [5]. Several FUS devices are investigated currently in clinical trials These devices can operate under image guidance to provide real-time monitoring of the treatment. Sonographic (ultrasound) guidance provides the benefit of imaging using the same form of energy that is being used for therapy The advantage of this is that the acoustic window can be verified with sonography. A recently introduced device is the transcranial MR-guided focused ultrasound This is a hemispheric phased-array transducer (ExAblate Neuro; InSightec Ltd., Tirat Carmel, Israel) with each element driven separately, providing individual correction of skull distortion as well as electronic steering. Essential tremor noninterventional functional neurosurgery treatment has shown an immense potential of transcranial MRgFUS application to induce lesions focally and treat patients nonsurgically [14]
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