Journal
EXPERIMENTAL EYE RESEARCH
Volume 189, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2019.107824
Keywords
Ocular drug delivery; Microneedles; Suprachoroidal space; Collagenase
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Funding
- National Institutes of Health [R01 EY022097, R01EY025286]
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Injection into the suprachoroidal space (SCS) allows drug delivery targeted to sclera, choroid, and retina. Here, we studied SCS injection formulated with collagenase to expand drug delivery coverage and increase posterior drug targeting within SCS by breaking down collagen fibrils that link sclera and choroid in the SCS. When 1 mu m latex microparticles were injected with a collagenase formulation using microneedles into the SCS of rabbit eyes ex vivo and incubated at 37 degrees C for 4 h, microparticle delivery coverage increased from 20% to 45% and enhanced posterior drug targeting. Collagenase concentration was optimized to 0.5 mg/mL to maximize expanded posterior delivery and minimize tissue damage. Effects of collagenase injection within SCS increased and then plateaued 4 h after injection. Simultaneous injection of collagenase and microparticles had a greater effect on expanded delivery in the SCS compared to sequential injection. Collagenase injection into the SCS of rabbit eyes in vivo was also effective to expand delivery and was generally well-tolerated, showing transiently lowered IOP, but no apparent lasting adverse effects on ocular tissues such as sclera, choroid, and retina, as determined by analyzing histology, sclera tensile strength, and fundus imaging. We conclude that addition of collagenase during SCS injection can expand drug delivery coverage and increase posterior drug targeting.
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