3D-printed long-acting 5-fluorouracil implant to prevent conjunctival fibrosis in glaucoma
To develop a sustained release 5-fluorouracil (5-FU) implant by three-dimensional (3D) printing to effectively prevent conjunctival fibrosis after glaucoma surgery.
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.
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.
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.
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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Nicole Ioannou, Jinyuan Luo, Mengqi Qin, Matteo Di Luca, Essyrose Mathew, Aristides D Tagalakis, Dimitrios A Lamprou, Cynthia Yu-Wai-Man, 3D-printed long-acting 5-fluorouracil implant to prevent conjunctival fibrosis in glaucoma, Journal of Pharmacy and Pharmacology, 2023;, rgac100,