Title:
Ocular drug delivery using microneedles

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dc.contributor.advisor Prausnitz, Mark R.
dc.contributor.author Jiang, Ninghao en_US
dc.contributor.committeeMember Allen, Mark
dc.contributor.committeeMember Edelhauser, Henry
dc.contributor.committeeMember Geroski, Dayle
dc.contributor.committeeMember Nickerson, John
dc.contributor.committeeMember Sambanis, Athanassios
dc.contributor.department Chemical Engineering en_US
dc.date.accessioned 2008-02-07T18:38:24Z
dc.date.available 2008-02-07T18:38:24Z
dc.date.issued 2006-11-21 en_US
dc.description.abstract Traditional methods of drug delivery to the eye include topical application, intraocular injection and systemic administration; however, each method has its limitation to efficiently delivery drugs to the back of the eye. In this study, microneedles were tested to provide targeted drug delivery into the eye in a minimally invasive way. To better interpret subsequent microneedle studies, we first quantified lateral drug diffusion profile within the sclera, by carrying out a diffusion study of a model compound, sulforhodamine, through human cadaver sclera, and developing a theoretical model for prediction of drug delivery kinetics and distribution. The results showed that measurable amounts of sulforhodamine were detected at distances of 5 and 10 mm from the sulforhodamine donor reservoir at 4 h and 3 days, respectively. The effective lateral diffusivity of sulforhodamine was determined to be 3.82 x 10-6 cm2/s, which is similar in magnitude to the transverse diffusivity. We next assessed the capability of using coated solid metal microneedles to deliver drugs into the ocular tissue in both in vitro and in vivo scenarios. The in vitro insertion tests showed that these microneedles were mechanically strong enough to penetrate into human cadaver sclera, and the coating solution rapidly dissolved off the needles after insertion and had been deposited within the tissue. In the in vivo experiments, microneedle delivery exhibited elevated fluorescein levels in the rabbit eye 60 times greater than that delivered by topical application of the equivalent dose. Similarly, microneedle delivery of pilocarpine caused rapid and extensive pupil constriction. Safety exams reported no inflammatory responses in the eye after microneedle administrations. We also used hollow glass microneedles to infuse solutions into the sclera tissue in vitro and examined the physiological barriers for flow. On average, 18 microliters of sulforhodamine solution and a solution containing nanoparticles was delivered into the sclera upon retraction of the microneedle. Successful delivery of micron-sized particles into the sclera could be improved by breaking down tightly packed collagen and GAG fibers using either collagenase or hyaluronidase. en_US
dc.description.degree Ph.D. en_US
dc.identifier.uri http://hdl.handle.net/1853/19796
dc.publisher Georgia Institute of Technology en_US
dc.subject Drug delivery en_US
dc.subject Eye en_US
dc.subject Microneedles en_US
dc.subject.lcsh Drug delivery devices
dc.subject.lcsh Eye
dc.subject.lcsh Hypodermic needles
dc.subject.lcsh Sclera
dc.title Ocular drug delivery using microneedles en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Prausnitz, Mark R.
local.contributor.corporatename School of Chemical and Biomolecular Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 4bd611de-763a-4e92-abdc-0558443485cc
relation.isOrgUnitOfPublication 6cfa2dc6-c5bf-4f6b-99a2-57105d8f7a6f
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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