The Analysis of Hyaluronic Acid as an Antifibrotic Agent and Drug Delivery Platform for 5FU

Abstract

Purpose: : 5-Fluorouracil injections have been used to prevent bleb failure and scarring. The aim of this study was to investigate the anti-scarring properties of hyaluronic acid (HA) on human Tenon’s myofibroblasts and the rate of 5FU release in a mixture with HA.

Methods: : Human Tenon’s fibroblasts pretreated with TGF-β were cultured with either HA alone or 5-FU/HA (HA concentrations10, 14, 23 mg/ml). Collagen I and alpha smooth muscle actin (ASMA) expression were quantified by RT-PCR. WST-1 assay determined cell viability. 5-FU solution or powder was dispersed in HA and mechanically stirred and then vortex mixed. Quantitation of 5-FU release was carried out by HPLC.

Results: : HA markedly reduced ASMA and collagen I mRNA expression by myofibroblasts compared to controls without HA. Treatment with HA following 5FU (10mg/ml) pretreatment resulted in a greater reduction in ASMA and collagen I expression compared to HA treatment alone, and statistical significance reached with 23mg/ml HA (p<0.05). Cell proliferation and viability was not affected by HA. 5FU solution mixed with HA delayed drug release to 48 hours, with HA of 14mg/ml and 23mg/ml showing a greater delay in drug release than 10mg/ml, (p<0.05). There was no significant difference in rate of drug release between powder and solution form of 5FU although the pH was notably different ie 6.6 and 10 respectively.

Keywords: wound healing • proliferation • drug toxicity/drug effects