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N. Jiang, D. Ghate, B.E. McCarey, D.H. Geroski, M.R. Prausnitz, H.F. Edelhauser; Scleral Drug Delivery Using Microneedles . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3881.
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To treat inflammatory and proliferative diseases in the posterior segment, it is difficult to deliver effective drug doses to the back of the eye using conventional delivery methods such as topical application and systemic administration. In this study, we adapted microfabrication technology to develop microscopic needles that penetrate just hundreds of microns into the sclera to deliver drugs to the back of the eye in a minimally invasive manner. We assessed whether (1) hollow microneedles could be used to microinject drug solution into the sclera and (2) solid microneedles coated with drug formulations could rapidly release their drug coatings by dissolution within ocular tissue.
To assess hollow microneedles for intrascleral microinjection, a hollow glass microneedle was inserted into human cadaver sclera for infusion of sulforhodamine solution at 5 – 20 psi. To assess solid microneedles for intraocular delivery, solid metal microneedles coated with sodium fluorescein were inserted into rabbit cornea in vivo. After needle removal, fluorescein concentration in the anterior segment was measured for ≤ 24 h.
Hollow microneedles were shown to insert into, but not across, human cadaver sclera and inject model drug solutions into the sclera. Microinjection volume increased with increasing pressure; up to 100 µl was injected within 5 mins at 20 psi. Solid metal microneedles were shown to insert into rabbit sclera in vivo. Sodium fluorescein completely dissolved off the needles within 3 min, which resulting in fluorescein concentrations in the anterior chamber 100 times greater that those achieved by topical delivery of fluorescein in the absence of microneedles. No inflammatory response or other adverse effects were observed when using microneedles.
For the first time, microneedles were shown to penetrate into sclera in vitro and cornea in vivo and to deliver useful quantities of model drugs into the ocular tissues. Microneedles may provide a minimally invasive method to deliver drugs into the sclera to treat diseases in the posterior segment that avoids the complications associated with intraocular injection and systemic administration.
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