Page 18 - JCTR-11-2

Journal of Clinical and
Translational Research US-mediated drug delivery

Table 4. Drug delivery with MB/ND‑assisted US for pre‑clinical studies in Alzheimer’s disease
References Drug, dye, Animal model US devices/parameters Targeted area MB/ND Therapy
particle duration
Choi et al., 2008 63 Gadolinium APP/PS1dE9 mouse Lab-made MRgFUS device; Left SonoVue MBs 1 sonication
®
1.525 MHz, DC 20%, 20 ms hippocampus (25 µL)
pulse duration, 0.6 MPa, for
1 min
Raymond et al., 2008 83 Anti-Aβ APP/PS1dE9 and Lab-made US device; Hippocampus Optison MBs 1 sonication
®
antibodies PDAPP mouse 0.69 MHz, 10 ms burst length, (30 – 50 µL)
1 Hz PRF, 0.67 – 0.8 MPa, for
40 – 45 s
®
Jordão et al., 2010 88 BAM-10 TgCRND8 mouse Lab-made US device; 0.3 MPa, Right Definity MBs 1 sonication
120 s, 10 ms bursts/Hz hemisphere (160 mL/kg)
®
Burgess et al., 2014 87 Gadolinium TgCRND8 mouse Lab-made US device; 10-ms Hippocampus Definity MBs 1 sonication
bursts, 1 Hz burst repetition (0.02 mL/kg) per week for
frequency, for 120 s 3 weeks
Nisbet et al., 2017 91 RN2N pR5 mouse Lab-made US device; 1 MHz, Whole brain Lab-made 1 sonication
10 Hz PRF, 0.7 MPa, 10 ms lipid-shelled per week for
pulse duration, DC 10%, for 6s MBs (30 µL) 4 weeks
Janowicz et al., 2019 92 RN2N pR5 mouse Lab-made US device; 1 MHz, Whole brain Lab-made 1 sonication
10 Hz PRF, 0.7 MPa, 10 ms lipid-shelled
pulse duration, DC 10%, for 6 s; MBs (40 µL)
Dubey et al., 2020 89 IVIg TgCRND8 mouse Lab-mad US device; 1 Hz burst Hippocampus Definity MBs 1 sonication
®
repetition frequency, 10 ms (0.02 mL/kg)
bursts, for 120 s
Liu et al., 2020 84 Quercetin APP/PS1dE9 mouse Lab-mad US device; 1 MPa for Parietal cortex Lab-made 1 sonication
5 min using a lipid-shelled per week for
MBs 5 weeks
Sun et al., 2021 85 Anti-pGlu3 Aβ APP/PS1dE9 mouse Lab-mad US device; 2 Hz, Hippocampus Optison MBs 1 sonication
®
10 ms bursts, for 100 s (100 µL/kg) per week for
3 weeks
Bathini et al., 2022 86 Anti-pGlu3 Aβ APP/PS1dE9 mouse Lab-mad US device; 2 Hz, One or two Lab-made 1 sonication
10 ms bursts, for 100 s hemispheres lipid-shelled
MBs
Kong et al., 2022 61 Aducanumab 5×FAD mouse Lab-mad US device; 1 Hz Hippocampus Definity MBs 1 sonication
®
burst, 0.25 MPa, 10 ms bursts, (0.04 mL/kg) every 2 weeks
for 120 s for a total of 3
Bajracharya et al., 2022 93 RNF5 K3 mouse Lab-made US device; 1 MHz, Whole brain Lab-made 1 sonication
10 Hz PRF, 0.7 MPa, 10 ms lipid-shelled per week for
pulse duration, DC 10%, for 6s; MBs (1 µL/g) 12 weeks
Gouveia et al., 2023 62 Pentobarbital TgCRND8 mouse Lab-made US device; 2 MPa, Amygdala Lab-made 1 sonication
10 ms bursts, 1 Hz, for 180 s NDs (0.1
mL/injection)
Antoniou et al., 2024 90 Anti-Aβ1 – 40 5×FAD mouse Lab-made US device; 1 MHz, Left SonoVue MBs 1 sonication
®
0.5 MPa in situ, 10 ms bursts, hemisphere (5 µL)
DF 1%, for 100 s
Abbreviations: DC: Duty cycle; MB: Microbubble; MRgFUS: Magnetic resonance imaging-guided focused ultrasound; ND: Nanodroplet; PRF: Pulse
repetition frequency; US: Ultrasound.

reversibility of repeated BBB opening in the frontal lobe changes were observed during the follow-up phase. The
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and hippocampus 94,95 of early-stage AD patients using the authors explained that the study primarily assessed safety
ExAblate Neuro Type 2 and Definity MBs. In a study by due to insufficient statistical power to detect clinical
®
®
Rezai et al., aducanumab was delivered through this US changes. The study reported one case of cognitive decline
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device, resulting in a significant reduction in Aβ plaque following aducanumab treatment and at least one case of
load. However, no neurological, cognitive, or behavioral severe adverse effects, which were deemed unrelated to
Volume 11 Issue 2 (2025) 12 doi: 10.36922/jctr.24.00061