Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): An Ex Vivo Study.
PURPOSE/AIM OF STUDY: Drug delivery to the ocular posterior segment is of importance, but it is a challenge in the treatment of irreversible blindness disease, such as age-related macular degeneration. Although some methods (i.e. intraocular injection, sustained release by polymer and iontophoresis) have been applied, some technical drawbacks, such as slow rate and damage to the eye, need to be overcome for wide use.


METHODS
In this study, the feasibility of high-intensity focused ultrasound (HIFU) to enhance the transsclera drug delivery was tested for the first time. One-hundred HIFU pulses with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration of 10-50 ms and pulse repetition frequency of 1 Hz were delivered to the fresh ex vivo porcine sclera specimen.


RESULTS
In comparison to the passive diffusion (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 ± 126.4 µm versus 252.4 ± 29.2 µm) using bicinchoninic acid assay and Rhodamine 6 G fluorescence intensity by 3.1 folds (22.4 ± 12.3 versus 7.1 ± 4.1) and coverage area by 2.6 folds (40.4 ± 9.1% versus 15.8 ± 2.9%). No morphological changes on the sonicated sclera samples were found using a surface electron microscope.


CONCLUSIONS
In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.
a Division of Engineering Mechanics , School of Mechanical and Aerospace Engineering, Nanyang Technological University , Singapore.
Suresh Kanna
SK
Murugappan
a Division of Engineering Mechanics , School of Mechanical and Aerospace Engineering, Nanyang Technological University , Singapore.
Yufeng
Y
Zhou
D000818:Animals; D001831:Body Temperature; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005456:Fluorescent Dyes / Q000008:administration & dosage*; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D007202:Indicators and Reagents / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D011804:Quinolines / Q000008:administration & dosage*; D012235:Rhodamines / Q000008:administration & dosage*; D012590:Sclera / Q000187:drug effects* / Q000648:ultrastructure; D013552:Swine; D014159:Transducers
D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D011804:Quinolines; D012235:Rhodamines; C026188:rhodamine 6G; C047117:bicinchoninic acid
Fluorescence; high-intensity focused ultrasound; penetration; pulse duration; transsclera drug delivery