ULTRASOUND-ASSISTED OCULAR DRUG DELIVERY
CORNEAL DELIVERYPoor absorption and high clearance from the ocular surface remain the main problems for the transepithelial delivery. We aimed to provide an enhanced clinical procedure of collagen crosslinking (CXL) without the removal of epithelium by ultrasound for non-invasive approach to increase permeability of epithelium. Ex-vivo experiments using porcine eyes had shown that ultrasound did improve the absorption of small molecules and proteins across the cornea epithelium with certain degree of penetration, compared to non-ultrasound treated. We will investigate further the optimization of ultrasound parameters that could give the best outcome in live rabbits.
|
|
|
SCLERAL DELIVERYDelivering to the posterior segment via the transscleral route is gaining popularity. It is proximal to the retina and circumvents the corneal epithelium and the lens. The outermost barrier along the transscleral path, the sclera, is a hydrated fibrous network of collagen, elastin and proteoglycan. It is permeable to hydrophilic molecules and even large molecules such as dextran, protein and nucleic acid. However, the low scleral permeability to macromolecules, together with the dynamic clearance by uveoscleral outflow and episcleral circulation, limits the utility of transscleral route for delivering therapeutics.
To increase the transscleral flux of macromolecules, we have proposed using ultrasound as a non-invasive approach to increase the permeability of sclera. From our animal studies, we demonstrated the feasibility of using low frequency and low intensity ultrasound to deliver macromolecules in to the eye along transscleral route. Visual function and eye structure were not disturbed after ultrasound treatment. We aim to further investigate the mechanism of ultrasound enhancement for transscleral drug delivery. |
Related publications
- Chau Y, Suen WL, Tse HY, Wong HS. "Ultrasound-enhanced penetration through sclera depends on frequency of sonication and size of macromolecules". European Journal of Pharmaceutical Sciences. 2017. Jan 16;100:273-279. doi: 10.1016/j.ejps.2017.01.016.
- Suen WL, Jiang J, Wong HS, Qu J, Chau Y. "Examination of Effects of Low-Frequency Ultrasound on Scleral Permeability and Collagen Network". Ultrasound in Medicine and Biology. 2016. Nov;42(11):2650-2661. doi: 10.1016/j.ultrasmedbio.2016.07.013.
- Suen, W.-L.L., Wong, H.S., Yu,Y., Lau, L.C.M., Lo, A.C.-Y., Chau, Y. “Ultrasound-mediated transscleral delivery of macromolecules to the posterior segment of rabbit eye in vivo” 2013. Investigative Ophthalmology & Visual Science. 54(6):4358-4365.