Enhancement of Drug Delivery in Prostate Tumor in vivo Using MR Guided Focused Ultrasound (MRgHIFU)

2009 ◽  
pp. 341-344 ◽  
Author(s):  
L. Chen ◽  
Z. Mu ◽  
P. Hachem ◽  
C. -M. Ma ◽  
A. Pollack
Keyword(s):  
Drug Delivery ◽  
Focused Ultrasound ◽  
Prostate Tumor

MR Guided Focused Ultrasound for Cancer Therapy: Enhancement of Drug Delivery in Prostate Tumor In Vivo

2008 ◽  
Vol 72 (1) ◽  
pp. S548-S549
Author(s):  
L. Chen ◽  
Z. Mu ◽  
P. Hachem ◽  
A. Konski ◽  
G. Freedman ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Focused Ultrasound ◽  
Prostate Tumor

scholarly journals Focused ultrasound blood brain barrier opening mediated delivery of MRI-visible albumin nanoclusters to the rat brain for localized drug delivery with temporal control

2019 ◽  
Author(s):  
Megan C. Rich ◽  
Jennifer Sherwood ◽  
Aundrea F. Bartley ◽  
Quentin A. Whitsitt ◽  
W.R. Willoughby ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Temporal Specificity ◽  
Blood Brain ◽  
Barrier Opening ◽  
Blood Brain Barrier Opening

AbstractThere is an ongoing need for noninvasive tools to manipulate brain activity with molecular, spatial and temporal specificity. Here we have investigated the use of MRI-visible, albumin-based nanoclusters for noninvasive, localized and temporally specific drug delivery to the rat brain. We demonstrated that IV injected nanoclusters could be deposited into target brain regions via focused ultrasound facilitated blood brain barrier opening. We showed that nanocluster location could be confirmed in vivo with MRI. Additionally, following confirmation of nanocluster delivery, release of the nanocluster payload into brain tissue can be triggered by a second focused ultrasound treatment performed without circulating microbubbles. Release of glutamate from nanoclusters in vivo caused enhanced c-Fos expression, indicating that the loading capacity of the nanoclusters is sufficient to induce neuronal activation. This novel technique for noninvasive stereotactic drug delivery to the brain with temporal specificity could provide a new way to study brain circuits in vivo preclinically with high relevance for clinical translation.Graphical Abstract

scholarly journals Enhanced Delivery and Bioactivity of the Neurturin Neurotrophic Factor through Focused Ultrasound—Mediated Blood—Brain Barrier Opening in vivo

2015 ◽  
Vol 35 (4) ◽  
pp. 611-622 ◽  
Author(s):  
Gesthimani Samiotaki ◽  
Camilo Acosta ◽  
Shutao Wang ◽  
Elisa E Konofagou
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Focused Ultrasound ◽  
Direct Injection ◽  
Brain Barrier ◽  
Injection Technique ◽  
Nigrostriatal Pathway ◽  
Blood Brain

The blood—brain barrier (BBB) constitutes a major obstacle in brain drug delivery. Focused ultrasound (FUS) in conjunction with microbubbles has been shown to open the BBB noninvasively, locally, and transiently to allow large molecules diffusion. Neurturin (NTN), a member of the glial-derived neurotrophic factor (GDNF) family, has been demonstrated to have neuroprotective and regenerative effects on dopaminergic neurons in vivo using invasive drug delivery methods. The brain's ascending nigrostriatal pathway is severely damaged in Parkinson's disease (PD), and therefore the substantia nigra (SN) and striatal caudoputamen (CP) were selected as the target areas. The objective of the study was to investigate whether safe and efficient NTN delivery can be achieved through FUS-induced BBB opening via intravenous administration, and thus trigger the neuroregeneration cascade in the nigrostriatal pathway. After the optimization of FUS parameters and target locations in the murine brain, NTN bioavailability and downstream signaling were detected and characterized through immunostaining. FUS significantly enhanced the delivery of NTN compared with the direct injection technique, whereas triggering of the signaling cascade was detected downstream to the neuronal nuclei. These findings thus indicate the potential of the FUS method to mediate transport of proteins through the blood—brain barrier in a PD animal model.

scholarly journals Ultrasound mediated delivery of quantum dots from a proof of concept capsule endoscope to the gastrointestinal wall

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fraser Stewart ◽  
Gerard Cummins ◽  
Mihnea V. Turcanu ◽  
Benjamin F. Cox ◽  
Alan Prescott ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Small Intestine ◽  
Oral Delivery ◽  
Focused Ultrasound ◽  
Living Organism ◽  
Therapeutic Agents ◽  
Proof Of Concept ◽  
Biologic Drugs ◽  
Fluorescent Markers

AbstractBiologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focused ultrasound during in vivo experiments using porcine models. This study illustrates how such a device could be potentially used for gastrointestinal drug delivery and the challenges to be overcome before focused ultrasound and microbubbles could be used with this device for the oral delivery of biologic therapeutics.

scholarly journals Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

2016 ◽  
Vol 37 (4) ◽  
pp. 1236-1250 ◽  
Author(s):  
Carlos Sierra ◽  
Camilo Acosta ◽  
Cherry Chen ◽  
Shih-Ying Wu ◽  
Maria E Karakatsani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Targeted Drug Delivery ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Inertial Cavitation ◽  
Blood Brain ◽  
Targeted Drug ◽  
Cavitation Detection

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

scholarly journals Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters

2018 ◽  
Author(s):  
Q Zhong ◽  
BC Yoon ◽  
M Aryal ◽  
JB Wang ◽  
A Karthik ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Focused Ultrasound ◽  
Drug Loading ◽  
The Body ◽  
Clinical Translation ◽  
Drug Infusion ◽  
Targeted Drug ◽  
Perfluorocarbon Nanoemulsions

ABSTRACTCatheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.

WE-G-220-04: Enhanced Uptake of Doxorubicin in Prostate Tumor Using Pulsed Focused Ultrasound - An in Vivo Study

2011 ◽  
Vol 38 (6Part34) ◽  
pp. 3838-3838
Author(s):  
X Chen ◽  
D Cvetkovic ◽  
C-M Ma ◽  
L Chen
Keyword(s):  
Focused Ultrasound ◽  
Prostate Tumor ◽  
In Vivo Study ◽  
Pulsed Focused Ultrasound
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