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Y. Jiang, W. Zheng, D. Su, R. Su, T. Aung, S. Venkatramen, T. T. Wong; The Analysis of Hyaluronic Acid as an Antifibrotic Agent and Drug Delivery Platform for 5FU. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4148.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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