[Non-biodegradable drug-sustained capsular ring for prevention of secondary cataract. Part I: In vitro evaluation].
OBJECTIVE
The appearance of secondary cataract constitutes the most common complication of cataract surgery since the advent of phacoemulsification. Prevention is today one of the most crucial challenges of research in ophthalmology. We have developed a drug-sustained capsular ring releasing 5-fluorouracil (5-FU). This system aims to combine mechanical and pharmacological properties with the ability to interfere on the lens epithelial cellular processes of secondary cataract. This first article will report on the in vitro evaluation of this system.


METHODS
Development of a hydrogel that can serve as a mechanical support and as a release of an active agent requires a comparative trial of multiple hydrophobic products providing rigidity to the ring and of hydrophilic products providing the ability to release a drug. The choice of 5-FU as a non-proliferate agent was based on its well-known pharmacological properties and its wide use in ophthalmology. Evaluation comprised adjustment of the adequate copolymer, then of the loading phase, and finally assessment of 5-FU release. The mechanical characteristics and cytocompatibility of the ring were also assessed.


RESULTS
The characteristics of drug release differed depending on the water content and resulting volume of the copolymer. The pharmaceutical and mechanical testing led to selecting the HPMA-MMA combination (75:25). However, a burst effect within the first 2 hours was observed in all cases. That limit was eliminated by creating a biodegradable surface coating of Poly Lactid-co-Glycolid (PLG 50:50) that could provide a positive barrier effect against migration and a controlled continual release of 0.25 microg/h extended to 9 days. Mechanical tests of tension, compression, and traction showed the crucial influence of the ring's hydration state. The cytocompatibility study showed no evidence of cellular toxicity.


CONCLUSIONS
The synthesized copolymer is able to release a constant, regular and safe rate of 5-FU, higher than CI50 over a period of 9 days for a cell proliferation phase of 3-5 days. We adjusted the ring associating the mechanical properties and the ability to release 5-FU, allowing further evaluation on animal models, the subject of the second part of this report.
Service d'Ophtalmologie, CHU Morvan, 5, avenue Foch, 29 609 Brest Cedex, France. beatrice.cochener-lamard@univ-brest.fr
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D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002386:Cataract / Q000517:prevention & control*; D002387:Cataract Extraction / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008689:Methacrylates; D012008:Recurrence
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D008689:Methacrylates; C005044:hydroxyethyl methacrylate; D005472:Fluorouracil