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Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery

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Abstract

Aim: To determine the release characteristics of a 5-fluorouracil-loaded poly (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the success of glaucoma nitration surgery in rabbit eyes. Methods: A method of microspheres accumulated by excessive carriers was used in the preparation of the 5-FU-PLA-DS. The disc was characterized for drug loading, entrapment efficiency, in vitro release, and external morphology. It was then implanted sub-conjunctivally into rabbit eyes with trabeculectomy. Intraocular pressure, ocular inflammatory reaction, filtration bleb appearance, and persistence were evaluated up to postoperative d 90. A quantitative analysis of 5-fluorouracil (5-FU) was performed in the aqueous humor. Ultrasound biomicroscopy was used to assess the appearance of the filtering fistula. Results: The 5-FU-PLA-DS was produced with the drug-loading of 3.07±0.08 mg (mean±SD). 5-FU was released for 91 d with suppressive concentrations. The decrease in intraocular pressure from baseline was significantly more marked in the 5-FU-PLA-DS-implanted eyes during postoperative d 3-90, and the persistence of bleb and filtration fistula was longer than the control eyes (P<0.05). Corneal toxicity and hyperemia triggered by 5-FU was lower in the 5-FU-PLA-DS-implanted eyes than those exposed to 5-FU intraoperatively. The 5-FU concentration in the aqueous humor was insufficient for corneal endothelial damage. No evidence of toxic reaction was found in the conjunctival biopsy. Conclusion: 5-FU-PLA-DS displaying sustained intraocular release of 5-FU, reduced intraocular pressure, and prolonged bleb persistence, while significantly reducing 5-FU toxicity.
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Keywords: 5-fluorouracil; glaucoma; intraocular pressure; microsphere; polymer; rabbit; sustained release

Document Type: Research Article

Affiliations: 1: Department of Ophthalmology, Xi-an Jiaotong University, Xi-an 710004, China 2: Department of Pharmacology, Xi-an Jiaotong University, Xi-an 710004, China

Publication date: 2008-09-01

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