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Related Experiment Videos

Ocular delivery using poly(ortho esters).

Jorge Heller1

  • 1PO Box 3519, Ashland, OR 97520, USA. jorgeheller2@aol.com

Advanced Drug Delivery Reviews
|November 18, 2005
PubMed
Summary
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Poly(ortho esters) show promise for controlled delivery of 5-fluorouracil (5-FU) in glaucoma treatment. Different polymer formulations offer tunable release rates and excellent ocular biocompatibility, maintaining low intraocular pressure effectively.

Area of Science:

  • Biomaterials Science
  • Ophthalmology
  • Drug Delivery Systems

Background:

  • Glaucoma filtering surgery often requires adjunct therapy to manage intraocular pressure.
  • 5-fluorouracil (5-FU) is an antiproliferative agent used in glaucoma treatment.
  • Poly(ortho esters) (POEs) are being explored for controlled drug delivery applications.

Purpose of the Study:

  • To investigate three families of poly(ortho esters) (POEs) for the controlled delivery of 5-fluorouracil (5-FU).
  • To evaluate the release kinetics, biocompatibility, and efficacy of POE-based 5-FU formulations in ocular applications.
  • To assess the potential of POE delivery systems for sustained intraocular pressure reduction post-glaucoma surgery.

Main Methods:

  • Synthesis and characterization of three families of poly(ortho esters) (POE II, POE III, POE IV).

Related Experiment Videos

  • In vitro studies to determine 5-FU release profiles from different POE formulations (linear, crosslinked, viscous, solid).
  • In vivo studies involving subconjunctival, intravitreal, suprachoroidal, and intracameral injections in rabbits to assess biocompatibility, polymer degradation, and efficacy in maintaining low intraocular pressure after trabeculectomy.

    • Main Results:

    • Release of 5-FU from POE II was diffusion-controlled, while linear POE II showed surface erosion.
    • POE III demonstrated tunable 5-FU release based on molecular weight and hydrophobicity, with excellent biocompatibility and 1-3 week lifetimes.
    • POE IV formulations (solid and viscous) provided controlled erosion-based 5-FU release with excellent biocompatibility and extended lifetimes (5 weeks to over 6 months depending on injection site).
    • Sustained 5-FU release from POE formulations effectively maintained low intraocular pressure in rabbits for up to 1 month post-trabeculectomy.

    Conclusions:

    • Poly(ortho esters) are effective and biocompatible vehicles for sustained ocular delivery of 5-fluorouracil.
    • Formulation parameters (e.g., molecular weight, hydrophobicity, physical form) allow for control over drug release rates and degradation profiles.
    • POE-based 5-FU delivery systems show significant potential for improving outcomes in glaucoma surgery by providing localized, sustained therapeutic drug levels.