Intrascleral drug delivery to the eye using hollow microneedles.
OBJECTIVE
This study tested the hypothesis that hollow microneedles can infuse solutions containing soluble molecules, nanoparticles, and microparticles into sclera in a minimally invasive manner.


METHODS
Individual hollow microneedles were inserted into, but not across, human cadaver sclera and aqueous solutions containing sulforhodamine or fluorescently tagged nanoparticles or microparticles were infused into sclera at constant pressure. The infused volume of fluid was measured and imaged histologically as a function of scleral thickness, infusion pressure, needle retraction depth and the presence of spreading enzymes (hyaluronidase and collagenase).


RESULTS
Individual hollow microneedles were able to insert into sclera. Fluid infusion was extremely slow after microneedle insertion into the sclera without retraction, but partial retraction of the microneedle over a distance of 200-300 microm enabled infusion of 10-35 microl of fluid into the tissue. Scleral thickness and infusion pressure had insignificant effects on fluid delivery. Nanoparticle suspensions were also delivered into sclera, but microparticles were delivered only in the presence of hyaluronidase and collagenase spreading enzymes, which suggested the role of scleral glycosaminoglycans and collagen fibers as rate-limiting barriers.


CONCLUSIONS
This study shows that hollow microneedles can infuse solutions into the sclera for minimally invasive delivery of soluble molecules, nanoparticles and microparticles.
Jiang
Jason
J
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA 30332-0100, USA.
Moore
Jason S
JS
Edelhauser
Henry F
HF
Prausnitz
Mark R
MR
D002102:Cadaver; D017364:Collagenases / Q000378:metabolism; D004867:Equipment Design; D024022:Fibrillar Collagens / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D066298:In Vitro Techniques; D008845:Microinjections / Q000295:instrumentation*; D053758:Nanoparticles; D009339:Needles; D010316:Particle Size; D011312:Pressure; D012235:Rhodamines / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*
D024022:Fibrillar Collagens; D006025:Glycosaminoglycans; D012235:Rhodamines; D006821:Hyaluronoglucosaminidase; D017364:Collagenases; C417249:collagenase 1