March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Biocompatibility Of A Novel Ocular Drug Delivery System
Author Affiliations & Notes
  • Nathan Gooch
    University of Utah, South Jordan, Utah
  • Michael Burr
    University of Utah, South Jordan, Utah
  • Bruce Gale
    Mechanical Engineering,
    University of Utah, South Jordan, Utah
  • Balamurali Ambati
    University of Utah, South Jordan, Utah
  • Footnotes
    Commercial Relationships  Nathan Gooch, None; Michael Burr, None; Bruce Gale, None; Balamurali Ambati, None
  • Footnotes
    Support  NIH Grant EY017185-01A2
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 435. doi:
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      Nathan Gooch, Michael Burr, Bruce Gale, Balamurali Ambati; Biocompatibility Of A Novel Ocular Drug Delivery System. Invest. Ophthalmol. Vis. Sci. 2012;53(14):435.

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

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Purpose: : To determine ocular biocompatibility of a novel, sustained release, refillable intraocular, drug delivery device.

Methods: : The intraocular drug delivery device is a reservoir and delivery agent which is designed to be placed within the capsular bag during cataract surgery. The capsule drug ring (CDR) prototypes were manufactured by hot melt extrusion of Bionate II® (DSM), a polycarbonate urethane. As the Bionate II® tubing was extruded from the dye, it was wrapped around a 8mm pipe to incorporate the correct inner and outer diameters into the polymer before fully setting. A filter composed of polyether sulfone was fitted to one end of the devices for controlled drug release. The other end was sealed. The devices have been optimized using Avastin® as the drug of interest. In vitro biocompatibility was assessed with human lens epithelial cell (B-3), mouse macrophage (J774A.1), and mouse fibroblast (L-929) cell lines. Cell migration and proliferation were assessed after in vitro culture. Pro-inflammatory cytokines (i.e. MIP-1β, MIP-1α, MCP-1, IL-1β, TNF, TGF-β1) were quantified using cytometric bead array (CBA). Preliminary in vivo biocompatibility and pharmacokinetics testing has been performed in rabbits.

Results: : The use of hot melt extrusion for CDR manufacture in place of previous design methodologies has dramatically improved the performance and reproducibility of drug delivery and pharmacokinetics. The devices have been designed to be a circular ring shape so as to fit in the capsular bag without impeding vision and have a drug reservoir of 50µL. In vitro cell migration and proliferation experiments show that the CDR components and devices had no measurable cytotoxic impact on B-3, J774A.1, and L-929 cell lines. Pro-inflammatory cytokine concentrations were also unchanged by the use of CDR device materials when compared to the gold standard tissue culture polystyrene cultured cells. Manufacturing methods were shown to be sterile as LPS was detected at levels below 0.0303 EU/mL. Preliminary in vivo histology shows Avastin® concentrations in the retina out to >90 days with very little host foreign body or inflammatory response.

Conclusions: : The results show the successful manufacture of the CDR, a potentially refillable drug delivery device. In vitro results show the devices and their individual components to be highly biocompatible with cells showing no difference in migration, proliferation, and pro-inflammatory cytokine generating behaviors. Avastin® was used as the primary drug of interest to test pharmacokinetics in vivo. Histology showed that the CDR devices performed as designed with very good biocompatibility. The CDR shows great potential as an implantable ocular device for drug delivery.

Keywords: age-related macular degeneration • inflammation • drug toxicity/drug effects 

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