3D-printed long-acting 5-fluorouracil implant to prevent conjunctival fibrosis in glaucoma

Objectives

To develop a sustained release 5-fluorouracil (5-FU) implant by three-dimensional (3D) printing to effectively prevent conjunctival fibrosis after glaucoma surgery.

Methods

3D-printed implants composed of polycaprolactone (PCL) and chitosan (CS) were fabricated by heat extrusion technology and loaded with 1% 5-FU. Light microscopy and scanning electron microscopy were used to study the surface morphology. The 5-FU concentration released over 8 weeks was measured by ultraviolet visible spectroscopy. The effects on cell viability, fibroblast contractility and the expression of key fibrotic genes were assessed in human conjunctival fibroblasts.

Key findings

The PCL–CS-5-FU implant sustainably released 5-FU over 8 weeks and the peak concentration was over 6.1 μg/ml during weeks 1 and 2. The implant had a smooth surface and its total weight decreased by 3.5% after 8 weeks. The PCL–CS–5-FU implant did not affect cell viability in conjunctival fibroblasts and sustainably suppressed fibroblast contractility and key fibrotic genes for 8 weeks.

Conclusions

The PCL–CS–5-FU implant was biocompatible and degradable with a significant effect in suppressing fibroblast contractility. The PCL–CS–5-FU implant could be used as a sustained release drug implant, replacing the need for repeated 5-FU injections in clinic, to prevent conjunctival fibrosis after glaucoma surgery.

Materials

Polycaprolactone powder (MW 50000 Daltons; Tm = 58°C; PCL) was supplied by Polysciences Inc. The low molecular weight chitosan powder (deacetylation degree ≥ 75%; Tm = 102.5°C; CS) and the 5-Fluorouracil (MW 130.08 g/mol; sparingly soluble in water <1 mg/ml; ≥ 99% HPLC; Tm = 282°C; 5-FU) were purchased from Sigma-Aldrich.

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