April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Nanoparticle Delivery of Ocular Hypotensive Compounds
Author Affiliations & Notes
  • Grace C. Shih
    Vanderbilt Eye Institute,
    Vanderbilt University, Nashville, Tennessee
  • Eva M. Harth
    Chemistry and Pharmacology,
    Vanderbilt University, Nashville, Tennessee
  • Brian J. Carlson
    Vanderbilt Eye Institute,
    Vanderbilt University, Nashville, Tennessee
  • David J. Calkins
    Vanderbilt Eye Institute,
    Vanderbilt University, Nashville, Tennessee
  • Footnotes
    Commercial Relationships  Grace C. Shih, None; Eva M. Harth, None; Brian J. Carlson, None; David J. Calkins, None
  • Footnotes
    Support  Melza and Theodore Barr and Glaucoma Research Foundations (DJC), NEI Core Grant (5P30EY008126-19), Research to Prevent Blindness Inc., Departmental Unrestricted Grant
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3079. doi:
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      Grace C. Shih, Eva M. Harth, Brian J. Carlson, David J. Calkins; Nanoparticle Delivery of Ocular Hypotensive Compounds. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3079.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. However, a major treatment barrier is patient compliance with use of topical agents to manage IOP, thus prompting a search for protracted therapeutic options. Recently, nanoparticles have been used for targeted drug delivery in chemotherapeutics, but have yet to be employed in ocular indications. To address the need for extended-release treatments, we examined the efficacy of nanoparticle-encapsulated compounds administered intravitreally to lower IOP in mice with microbead-induced ocular hypertension.

Methods: : We constructed 400 and 700 nm nanoparticle sponges encapsulating bimatoprost (22.4% and 29.35 %, respectively) at 14% cross-linking density. C57BL/6 mice received a bilateral injection of microbeads (1.5 ul) into the anterior chamber to elevate IOP, followed by an intravitreal injection (1.0 ul) of either bimatoprost-encapsulating nanoparticles or PBS. IOP was measured by tonopen in both eyes up to 47 days post-injection.

Results: : Microbead injections elevated IOP bilaterally 40-43% above baseline measurements of 13-14 mmHg. A single injection of 400nm bimatoprost nanoparticles lowered IOP to baseline for two weeks followed by a gradual return to elevated levels by day 25. In contrast, 700nm bimatoprost nanoparticles lowered IOP for five weeks followed by a gradual return to elevation by day 48. Both hypotensive effects were highly significant (p<0.001).

Conclusions: : Nanoparticle sponges encapsulating bimatoprost, when injected intravitreally, are effective at reducing elevations in IOP induced by microbead injection into the anterior chamber. Increasing particle size prolonged IOP reduction. This suggests that intravitreal injections of therapeutically-loaded nanoparticles may be a long-term drug delivery solution for glaucoma.

Keywords: intraocular pressure • neuroprotection • retina 

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