Page 21 - JCTR-11-2

Journal of Clinical and
Translational Research US-mediated drug delivery

Table 6. Drug delivery with MB‑assisted US for pre‑clinical studies in Parkinson’s disease
References Drug, dye, Animal model US devices/ Targeted area MBs Therapy duration
particle parameters
Fan et al., 2016 105 GDNF 6-OHDA rat Lab-made US device; Substantia nigra and Lab-made 1 sonication
1-MHz, 1 Hz PRF, striatum lipid-shelled MBs
0.7 MPa, 5,000
cycles)
Lin et al., 2016 107 GDNF MPTP mouse Lab-made US device; Substantia nigra Lab-made Sonication twice a
0.3 – 0.8 MPa, 10 ms lipid-shelled MBs week for 3 weeks
burst length, 1 Hz
PRF, for 60 s
Zhang et al., 2018 108 Curcumin MPTP mouse Lab-made US device; Corpus striatum in Lab-made 1 sonication every
60s medial forebrain lipid-shelled MBs 2 days for 4 times
bundle (MFB)
®
Xhima et al., 2018 114 shRNA Transgenic mouse Lab-made US device; Hippocampus, Definity MBs 1 sonication
against overexpression 10 ms bursts, 1 Hz substantia nigra, (0.02 mL/kg)
α-synuclein α-synuclein gene PRF, for 120 s olfactory bulb, and
dorsal motor nucleus)
Yue et al., 2018 106 GDNF 6-OHDA rat Lab-made US device; Right substantia nigra Lab-made Once every 3 days,
1 MHz, DC 20%, lipid-shelled MBs sacrificed at 3 weeks
2
2 W/cm intensity (0.01 mL/kg) after treatment
Karakatsani et al., 2019 109 GDNF MPTP mouse Lab-made US device; Caudate-putamen Lab-made 1 sonication
10 Hz PRF, 0.45 MPa, and ventral midbrain lipid-shelled MBs
for 60 s region (0.1 µL/g)
Lin et al., 2020 110 BDNF MPTP mouse Lab-made US device; Substantia nigra Lab-made Sonication twice a
1 MHz, 10 ms burst lipid-shelled MBs week for 3 weeks
length, 10 Hz PRF, (10 µL)
for 3 min
Feng et al., 2022 113 Triptolide Transgenic mouse Lab-made US Substantia nigra Lab-made Sonication twice a
overexpression device; 10 ms burst lipid-shelled MBs week for 3 weeks
α-synuclein gene length, 1 Hz PRF, (100 µL)
0.3 – 0.8 MPa, for 60 s
®
Wang et al., 2022 112 Gastrodin MPTP mouse Lab-made US device; Left striatum SonoVue MBs Sonication once
10 ms pulse width, (1.125 µL/g) every 3 days for
1 Hz, PRF, for 60 s 6 times
Blesa et al., 2023 111 AAV9-hSyn 6 male macaque Lab-made US device; Striatum and Luminity MBs 1 sonication
®
-GFP monkeys for 60 s midbrain (4 µL/kg/mL,
0.02 mL/s)
Abbreviations: DC: Duty cycle; MB: Microbubble; PRF: Pulse repetition frequency; US: Ultrasound; BDNF: brain-derived neurotrophic factor.
three treatment sessions every 2 weeks over 5 weeks. GCase well as significant improvement in movement disorders in
was administered at escalating doses (15, 30, and 60 lU/kg) PD patients (Table 7).
through i.v. infusion over 1 h, followed by the infusion of
Definity MBs (4 µL/kg/5 min). US waves were applied 7. Applications in ALS
®
using the ExAblate Neuro MRgFUS system (10 ms pulses, 7.1. ALS
®
DC 1%, 0.5 MPa, for 2 min). The efficacy of acoustically
mediated BBB opening was monitored using DCE-MRI. ALS, also known as Charcot’s disease, is a
Motor performance was evaluated between treatments neurodegenerative disease that affects both upper and
and 1, 3, and 6 months post-treatment, with 18F-FDG lower motor neurons (UMN and LMN) in the motor
PET imaging and mental examination performed 1 month cortex, brainstem, and spinal cord. This degeneration
and 3 months after the final treatment. Results supported is irreversible and progressive, leading to a relentless
the safety and feasibility of this approach. BBB opening decline in motor functions. The prevalence of ALS
facilitated the targeted delivery of GCase, leading to reduced is approximatively 1 – 2/100,000 individuals and the
putaminal hypermetabolism 1 month after treatment, incidence is 6 – 8/100,000 people/year. 76,122 ALS manifests
reflecting improved striatal dopaminergic metabolism, as in different forms depending on the location of the

Volume 11 Issue 2 (2025) 15 doi: 10.36922/jctr.24.00061