Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery.
OBJECTIVE
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.


CONCLUSIONS
5-FU-PLADS displaying sustained intraocular release of 5-FU, reduced intraocular pressure, and prolonged bleb persistence, while significantly reducing 5-FU toxicity.
Cui
Li-jun
LJ
Department of Ophthalmology and Pharmacology, Xi-an Jiaotong University, Xi-an 710004, China.
Sun
Nai-xue
NX
Li
Xing-hua
XH
Huang
Jie
J
Yang
Jian-gang
JG
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage* / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use*; D020327:Glaucoma Drainage Implants; D007202:Indicators and Reagents; D007429:Intraocular Pressure / Q000187:drug effects; D019344:Lactic Acid; D008863:Microspheres; D013508:Ophthalmologic Surgical Procedures; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019919:Prosthesis Implantation; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D016019:Survival Analysis
D000963:Antimetabolites; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007202:Indicators and Reagents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005472:Fluorouracil