A novel antiproliferative drug coating for glaucoma drainage devices

J Glaucoma. 2014 Oct-Nov;23(8):526-34. doi: 10.1097/IJG.0b013e318294869b.

Abstract

Purpose: The implantation of a glaucoma drainage device (GDD) is often necessary for intractable cases of glaucoma. Currently, the success rate of GDD implants is relatively low because fibrosis that develops during the wound-healing process ultimately blocks fluid drainage. We describe herein a novel porous coating for Ahmed glaucoma valves based on biodegradable poly(lactic-co-glycolic acid) (PLGA).

Materials and methods: Thin films of PLGA were fabricated using a spin-coating technique. The procedure led to an asymmetric pore structure that was exploited to control the rate of dissolution. Double-layered porous films were constructed to achieve continuous drug release. A cell culture system was used to test the efficacy of these coatings.

Results: Double-layered films were manufactured to provide a burst of mitomycin C (MMC) release followed by a slow release of 5-fluorouracil (5-FU), which together prevented fibrosis over the most active period of postoperative wound healing (0 to 28 d). Double-layered films containing 5-FU only in the bottom layer showed a 3- to 5-day delay in drug release, followed by a sharp increase that continued for ~28 days. MMC was stable only when surface-loaded, and this drug was therefore surface-loaded onto the top PLGA layer to provide a continuous release of antifibrotics over the wound-healing period.

Conclusions: The combined use of both MMC and 5-FU in a biodegradable device inhibits cell proliferation in a tissue culture model and has the potential to reduce fibrosis and increase the success rate of GDD implants. The design is simple and can be scaled for commercial production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Drug Delivery Systems
  • Fibrosis / etiology
  • Fibrosis / prevention & control
  • Fluorouracil / administration & dosage*
  • Fluorouracil / chemistry
  • Glaucoma / surgery*
  • Glaucoma Drainage Implants*
  • Lactic Acid / chemistry*
  • Mitomycin / administration & dosage*
  • Mitomycin / chemistry
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Mitomycin
  • Fluorouracil