Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery

• Published in: Acta pharmacologica Sinica Vol. 29; no. 9; pp. 1021 - 1028
• Main Authors: Cui, Li-jun, Sun, Nai-xue, Li, Xing-hua, Huang, Jie, Yang, Jian-gang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2008; Nature Publishing Group
• Subjects: 5-氟脲嘧啶; Animals; Antimetabolites - administration & dosage; Antimetabolites - therapeutic use; Aqueous Humor - drug effects; Aqueous Humor - metabolism; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid; Conjunctiva; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Female; Fluorouracil - administration & dosage; Fluorouracil - therapeutic use; Glaucoma; Glaucoma Drainage Implants; Immunology; Indicators and Reagents; Internal Medicine; Intraocular Pressure - drug effects; Lactic Acid; Medical Microbiology; Microspheres; Ophthalmologic Surgical Procedures; original-article; Particle Size; Pharmacology/Toxicology; Polyglycolic Acid; Prosthesis Implantation; Rabbits; Spectrophotometry, Ultraviolet; Survival Analysis; Vaccine; 微球; 眼内压; 聚合物; 青光眼; 5-fluorouracil; polymer; intraocular pressure; sustained release; glaucoma; rabbit; microsphere
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1111/j.1745-7254.2008.00833.x

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 filtration 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 subconjunctivally 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-DSimplanted 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.