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

Nicole Ioannou, Jinyuan Luo, Mengqi Qin, Matteo Di Luca, Essyrose Mathew, Aristides D Tagalakis, Dimitrios A Lamprou, Cynthia Yu-Wai-Man

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Abstract

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.
Original languageEnglish
JournalJournal of Pharmacy and Pharmacology
Early online date6 Jan 2023
DOIs
Publication statusE-pub ahead of print - 6 Jan 2023

Keywords

  • Pharmaceutical Science
  • Pharmacology

Research Institutes

  • Health Research Institute

Research Centres

  • Cardio-Respiratory Research Centre
  • Data Science STEM Research Centre

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