Table 3.
Summary of the methods used by included studies to facilitate ultrasound-mediated ocular drug delivery.
| Ref | Method of delivery | Delivery pathway | Animal model | Delivery assessment | Delivered compound | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MBPEXO | AS | MBPENDO | Trans-topical | Blood-retinal barrier | Vitreal/ Vitreoretinal | Direct injection into target tissue | Small rodent | Rabbit | Large Mammal | Coadministered microbubbles? |
Cavitation assessed using PCD (W/cm2) |
Streaming assessed experimentally |
Virus | Plasmid | siRNA | Small Molecule | Fluorophore/ contrast agent | Topical co-incubation time (min) | ||
| 69 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | Yes - contributed to delivery | - | - | - | ✓ | - | 60 | |
| 62 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | Stable @ 0.19-0.56Inertial @ 0.34-0.56 | Yes - contributed to delivery | - | - | - | - | ✓ | 5* | |
| 60 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | - | ✓ | 60 | |
| 36 | ✓ | - | - | - | - | - | ✓ | - | ✓ | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 37 | ✓ | - | - | - | - | - | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 64 | - | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | ✓ | - | - | ✓ | - | |
| 82 | ✓ | - | - | - | - | - | ✓ | ✓ | - | - | ✓ | - | - | ✓ | - | - | - | - | - | |
| 75 | ✓ | ✓ | - | - | ✓ | ✓ | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 38 | ✓ | - | - | - | - | - | ✓ | ✓ | - | - | ✓ | - | - | ✓ | - | - | - | - | - | |
| 77 | ✓ | - | - | - | ✓ | - | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 76 | - | ✓ | ✓ | - | ✓ | ✓ | - | ✓ | - | - | ✓ | - | - | - | - | - | ✓ | - | - | |
| 33 | ✓ | - | - | - | - | ✓ | - | ✓ | - | - | ✓ | - | - | ✓ | - | - | - | - | - | |
| 61 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | Stable @ all frequencies | Yes - contributed to delivery | - | - | - | - | ✓ | 5, 15, 30, 60 | |
| 28 | ✓ | - | - | - | - | - | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 154 | ✓ | - | - | - | - | ✓ | - | ✓ | - | - | ✓ | - | - | - | - | ✓ | - | ✓ | - | |
| 66 | ✓ | - | - | - | ✓ | - | - | ✓ | - | - | ✓ | - | - | - | - | - | - | ✓ | - | |
| 65 | ✓ | ✓ | - | - | - | ✓ | - | - | ✓ | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 34 | ✓ | ✓ | - | - | - | ✓ | - | ✓ | - | - | ✓ | - | - | ✓ | - | - | - | - | - | |
| 71 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | - | ✓ | 45 | |
| 70 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | ✓ | ✓ | 60 | |
| 39 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | - | ✓ | 6.5, 11.5, 16.5 | |
| 44 | ✓ | - | - | - | ✓ | - | - | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 16 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | ✓ | - | 5* | |
| 74 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | - | ✓ | 10, 20, 30, 40 | |
| 49 | - | ✓ | ✓ | ✓ | - | - | - | - | - | ✓ | - | - | - | - | - | - | - | ✓ | <1** | |
| 83 | ✓ | ✓ | - | - | - | ✓ | - | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 35 | ✓ | - | - | - | - | - | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | |
| 73 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | Stable @ 0.002 to 0.05Inertial at 0.38 to 1.8 | - | - | - | - | - | ✓ | 15 | |
| 46 | ✓ | ✓ | - | - | - | ✓ | - | - | ✓ | - | ✓ | - | - | - | - | - | ✓ | - | - | |
| 17 | ✓ | ✓ | - | - | - | ✓ | - | ✓ | - | - | ✓ | - | - | - | - | ✓ | - | ✓ | - | |
| 72 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | Stable @ all frequencies | Yes - contributed to delivery^ | - | - | - | - | ✓ | <1, 15 | |
| 40 | - | ✓ | ✓ | - | - | ✓ | - | - | - | ✓ | - | - | - | - | - | - | - | ✓ | - | |
| 41 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | - | - | - | - | - | - | - | - | ✓ | 60 | |
| 45 | - | - | ✓ | ✓ | - | - | - | ✓ | - | - | - | - | - | - | - | - | ✓ | ✓ | 10*** | |
| 42 | - | ✓ | - | - | - | ✓ | - | - | - | ✓ | ✓ | - | Yes - contributed to delivery | - | - | - | - | ✓ | - | |
| 15 | ✓ | - | - | - | ✓ | - | - | ✓ | - | - | ✓ | Depended on mouse^^ | - | ✓ | - | - | - | ✓ | - | |
| 43 | - | ✓ | ✓ | ✓ | - | - | - | - | ✓ | ✓ | - | - | - | - | - | - | ✓ | ✓ | 30, 120 | |
*Eye bath containing drug was removed after 5-minute sonication, however the eye was not rinsed after. **HIFU transducer. ***15 min sonication followed by drug. ^small molecules only. ^^Sonication pressures reported were not clearly defined.