June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Biocompatible injectable hydrogel to extend the release of intravitreal drugs
Author Affiliations & Notes
  • Thomas Friberg
    Ophthalmology/UPMC Eye Center, Univ of Pittsburgh, Pittsburgh, PA
    Bioengineering, University of Pittsburgh, Pittsburgh, PA
  • Britta Rauck
    Bioengineering, University of Pittsburgh, Pittsburgh, PA
  • Carlos Medina-Mendez
    Ophthalmology/UPMC Eye Center, Univ of Pittsburgh, Pittsburgh, PA
  • Yadong Wang
    Bioengineering, University of Pittsburgh, Pittsburgh, PA
  • Footnotes
    Commercial Relationships Thomas Friberg, 13/581,518 (P); Britta Rauck, None; Carlos Medina-Mendez, None; Yadong Wang, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4111. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Thomas Friberg, Britta Rauck, Carlos Medina-Mendez, Yadong Wang; Biocompatible injectable hydrogel to extend the release of intravitreal drugs. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4111.

      Download citation file:

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

  • Supplements

Purpose: An ideal drug delivery platform should be biocompatible, completely biodegradable, non-toxic, simple to administer, and extend the release of drugs several fold. We investigated the utility of a biocompatible gelling solution to deliver bevacizumab (Avastin) in rabbit eyes.

Methods: We synthesized poly((Ethylene glycol)-co) Serinol Hexamethalyne) Urethane (ESHU) to produce a liquid that could be injected through a 31-gauge needle and form a gel immediately upon entry into a hyaluronic acid solution at 35 degrees C, the temperature of human vitreous. We injected 50 μl of a 15% solution of ESHU containing either 1.25 mg or 4 mg of bevacizumab intravitreally into rabbit eyes to determine the release characteristics. We observed the fundus and measured intraocular pressure (IOP) at each sampling point. We withdrew aqueous samples from the eyes over 8 weeks’ time, and determined its bevacizumab concentration using an enzyme-linked immunosorbent (ELISA) assay. Histology of the rabbit eyes was obtained upon sacrifice.

Results: Using a standard 1.25 mg dose of bevacizumab in 0.05 ml of gelling solution, the polymer sustained the release of bevacizumab substantially for more than 6 weeks compared to less than 4 weeks in groups receiving free bevacizumab alone. With the concentrated dose, the aqueous concentration at 1 month was 7.7 mcg/ml compared to 0.47 mcg/ml in controls (1X concentration, no polymer). At 7 weeks’ time, 0.41 mcg/ml, an amount likely to be sufficient for VEGF suppression, was found in the rabbit eyes compared to a 0.07 mcg/ml in controls. An expected IOP spike occurred immediately following injection, and the IOP returned to baseline levels within 15 minutes time and remained normal throughout the study period. Histologically, there was no evidence of inflammation, affirming ESHU's biocompatibility.

Conclusions: ESHU appears to an efficient drug delivery platform which is non-toxic and can sustain the release of bevacizumab for more than 8 weeks after a single injection in a rabbit. In a human, this release would be most likely even slower, as the human eye is larger than the rabbit eye, 4 cc vs. 1.5 cc. As the polymer is an injectable solution, it can sustain the delivery of virtually any intravitreal medication; we expect similar release curves with other agents. One of the advantages of this hydrophobic and hydrophilic gel is that no polar solvents are required to load the drug into the delivery

Keywords: 412 age-related macular degeneration • 748 vascular endothelial growth factor • 503 drug toxicity/drug effects  

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.