The Journal of pharmacy and pharmacology · 2023
3D-printed long-acting 5-fluorouracil implant to prevent conjunctival fibrosis in glaucoma.
СтатьяНазвание и аннотация: Перевод в очереди
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Ioannou Nicole, Luo Jinyuan, Qin Mengqi, Di Luca Matteo, Mathew Essyrose, Tagalakis Aristides D, Lamprou Dimitrios A, Yu-Wai-Man Cynthia
Аннотация
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.
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.