A New Poly(Ortho Ester)-Based Drug Delivery System as an Adjunct Treatment in Filtering Surgery

• Published in: Investigative ophthalmology & visual science Vol. 42; no. 3; pp. 695 - 700
• Main Authors: Einmahl, Suzanne, Behar-Cohen, Francine, D'Hermies, Francois, Rudaz, Serge, Tabatabay, Cyrus, Renard, Gilles, Gurny, Robert
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01-03-2001; Association for Research in Vision and Ophtalmology
• Subjects: Animals; Anterior Eye Segment - pathology; Aqueous Humor - metabolism; Biocompatible Materials - administration & dosage; Biological and medical sciences; Chemotherapy, Adjuvant; Drug Delivery Systems; Eye; Female; Fluorouracil - administration & dosage; Fluorouracil - pharmacokinetics; Intraocular Pressure - drug effects; Medical sciences; Pharmacology. Drug treatments; Polymers - administration & dosage; Rabbits; Trabeculectomy; Wound Healing - drug effects; Antineoplastic agent; Trabeculectomy; Rabbit; Pyridine derivatives; Glaucoma (eye); Surgery; Biomaterial; Biological effect; Cicatrization; Fluorouracil; Delivery system; Enzyme; Transferases; Fluoropyrimidine derivatives; Enzyme inhibitor; Lagomorpha; Thymidylate synthase; Eye disease; Vertebrata; Chemotherapy; Mammalia; Methyltransferases; Antimetabolic; Animal; Orthoester; Pyrimidine derivatives; Combined treatment; Subconjunctival administration
• ISSN: 0146-0404; 1552-5783

Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(ortho ester) (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a sustained drug delivery system that allows the frequency of intraocular injections to be reduced. The purpose of this study was to determine the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit.
Trabeculectomy was performed in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt 5-FU was injected subconjunctivally at the site of surgery, during the procedure. Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the anterior chamber. Histologic analysis was used to assess the appearance of the filtering fistula and the polymer's biocompatibility.
The decrease in IOP from baseline and the persistence of the filtering bleb were significantly more marked in the 5-FU-treated eyes during postoperative days 9 through 28. Corneal toxicity triggered by 5-FU was significantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes treated with POE containing 5-FU.
In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bleb persistence in a way similar to the conventional method of a 5-FU tamponade, while significantly reducing 5-FU toxicity.