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M. R. Prausnitz, J. Jiang, S. R. Patel, H. S. Gill, D. Ghate, B. E. McCarey, D. H. Geroski, H. F. Edelhauser; Ocular Drug Delivery Using Microneedles. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3191.
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Traditional methods of ocular drug delivery include topical application, intraocular injection and systemic administration; however, each method has its difficulty to efficiently deliver drugs to the back of the eye. In this study, we adapted microfabrication technology to develop microscopic needles that penetrate just hundreds of microns into the ocular tissue via cornea or sclera to deliver drugs into the eye in a minimally invasive manner. We assessed whether (1) hollow microneedles could be used to microinfuse 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 infusions of sulforhodamine solution, nanoparticle suspension and microparticle suspension. 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. Similar experiments were repeated using pilocarpine-coated microneedles, and the rabbit pupil size was monitored afterwards.
Hollow microneedles were shown to insert into, but not across, human cadaver sclera and inject tens of microliters of model drug solutions and nanoparticle suspensions into the sclera. Successful delivery of micron-sized particles into the sclera could be improved by breaking down tightly packed collagen or GAG fibers using either collagenase or hyaluronidase. Solid metal microneedles were shown to insert into rabbit sclera in vivo. Sodium fluorescein completely dissolved off the needles within 30 sec, which resulting in fluorescein concentrations in the anterior chamber 70 times greater than those achieved by topical delivery of fluorescein without microneedles. Similarly, microneedle delivery of pilocarpine caused rapid and extensive pupil constriction. 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 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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