. 2021 Jul 9;13(7):1053. doi: 10.3390/pharmaceutics13071053

Table 4.

Preclinical and clinical studies using FUS for delivery of therapeutic agents to the brain parenchyma.

Preclinical
Animal Species/Therapeutic Agent	US Parameters	Key Findings	Ref.
Species: New Zealand white rabbits	Intensity: 16–690 W/cm² Pressure: 0.7–4.7 MPa Burst duration: 10 or 100 ms PRF: 1 Hz TT: 20 s	Low acoustic power levels were able to consistently enhance BBB permeability following administration of an US contrast agent No neuronal damage was observed at pressure amplitudes 0.7 and 1.0 MPa. Opening of the BBB was independent of burst duration and acoustic power.	[96]
Species: Orthotopic xenograft model Drug: Doxorubicin, ado-trastuzumab emtansine (T-DM1)	Frequency: 1 MHz Peak negative pressure (PNP): 480 kPa Burst duration: 10 ms every 1 s TT: 2 min	Extravasation of doxorubicin and T-DM1 was significantly increased using FUS in combination with microbubble contrast agent in comparison to non-FUS group via multiphoton microscopy (7-fold and 2-fold higher). Drug penetration was significantly increased in both treatment groups (>100 vs. <20 μm and 42 ± 7 vs. 12 ± 4 μm for doxorubicin and T-DM1).	[105]
Species: Fischer 344 rats Drug: TMZ	Power: 3 W PNP: 0.6 MPa Burst duration: 10 ms PRF: 1 Hz TT: 60 s	Accumulation of TMZ in CSF/plasma increased following FUS treatment (22.7% to 38.6%). Reduction in 7 day tumor progression ratio was observed following FUS treatment (24.03 to 5.06) Median survival was extended from 20 to 23 following FUS treatment.	[106]
Species: Sprague-Dawley rats Drug: liposomal doxorubicin	Pressure: 1.2 MPa Burst duration: 10 ms PRF: 1 Hz TT: 60–120 s	Reduction in tumor growth was observed in the FUS + DOX treated group in comparison to DOX alone (indicated by tumor volume doubling time 3.7 ± 0.5 days vs. 2.7 ± 0.4 days). A significant increase (>24%) in median survival was observed in FUS + DOX treated group in comparison to non-treated group (p = 0.0007).	[107]
Species: Nu/Nu mice Drug: BVZ	Frequency: 400 kHz PNP: 0.4–0.8 MPa Burst duration: 10 ms PRF: 1 Hz TT: 60 s	Penetration of BVZ into the CNS was statistically enhanced in the FUS + BVZ in comparison to BVZ alone (5.73-fold increase at 0.4 MPa and 56.7-fold increase at 0.8 MPa). Median survival time was significantly increased in FUS + BVZ treated group in comparison to BVZ alone (135% vs. 48%; p = 0.0002).	[108]