An intraocular lens coated with polycaprolactone and methotrexate as a slow-release system for prophylaxis of posterior capsule opacification in-vitro.

PURPOSE: Posterior capsule opacification (PCO) is the most common postoperative complication after cataract surgery. As a pharmacological prophylaxis, we designed a drug-carrying slow-release intraocular lens (IOL) implant coated with polycaprolactone and methotrexate and characterized the release kinetics and the in-vitro effect.

METHODS

Electron microscopy was used to image the coated IOL and a pharmacodynamic eye model to determine the release kinetics. FHL 124 cells were exposed to the coated IOL for 48 h and the effect was determined by migration (Boyden chamber, scratch assay), proliferation (BrdU ELISA), extracellular matrix contraction (collagen lattice assay), protein expression (immunofluorescence staining, Western blot analysis, proteomics), and toxicity (WST-1 assay, live/dead staining). Growth in the human capsular bag was assessed after IOL implantation.

RESULTS

Electron microscopy confirmed the drug carrier design without altering the IOL polymer. A concentration of methotrexate above 200 nM was maintained for approximately 120 days. The cells exposed to the loaded IOL showed significantly reduced migration (p = 0.04; p = 0.0005), proliferation (p = 0.0098), and matrix contraction (p = 0.02). Markers of fibrosis (collagen type 1, fibronectin, and vimentin) were inhibited. Proteins associated with protein and RNA expression, metabolism and mitochondrial genes were significantly regulated. No change in viability was observed. The coated IOL induced significantly slower growth in the human capsular bag (p = 0.04) and immunofluorescence staining was consistent with FHL 124 staining.

CONCLUSION

The proposed IOL showed favourable release kinetics and attenuated the main features of PCO formation, making it a prophylactic option with clinical potential.