Development of a drug-eluting intraocular lens to deliver epidermal growth factor receptor inhibitor gefitinib for posterior capsule opacification prophylaxis

Abstract

Purpose: Different molecular targets, such as the epidermal growth factor receptor, have been identified for the prophylaxis of posterior capsule opacification. This led to the proposal of several drugs, yet drug delivery into the capsular bag remains challenging. The intraocular lens as a drug delivery device would provide a convenient method to allow drug release in the location needed. This is to evaluate the effect of a drug-eluting intraocular lens using an epidermal growth factor receptor inhibitor. Methods: Hydrophobic and hydrophilic intraocular lenses were coated with gefitinib using the dip coating technique. The cellular response on the modified intraocular lenses was tested in a human lens epithelial cell line (FHL-124) in an anterior segment model. Furthermore, modified intraocular lenses were implanted into human capsular bags ex vivo. Drug release was determined as well as the biocompatibility on human corneal endothelial cells. Unmodified intraocular lenses served as controls. In addition, immunofluorescence staining with fibronectin as a marker for fibrotic response was conducted. Results: Both coated hydrophilic and hydrophobic intraocular lenses could attenuate the cell growth of FHL-124 cells in the human capsular bag in comparison to the unmodified controls. Furthermore, gefitinib-soaked intraocular lenses showed a constant drug release over the first 10 days. No reduction in cell viability of corneal endothelial cells occurred. A decrease in fibronectin expression under gefitinib treatment could be observed. Conclusion: In vitro epidermal growth factor receptor seems to be a valuable target for the prevention of posterior capsule opacification. The gefitinib-eluting intraocular lens in this study could inhibit cell growth in non-toxic concentrations.

Therapeutic Ophthalmic Lenses: A Review

“…The simplest method for obtaining therapeutic lenses is soaking into a drug solution [ 24 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. The amount of drug loaded and released depends on the material and the structure of the lens (e.g., porosity, swelling capacity), on the drug characteristics (e.g., molecular structure, molecular weight, charge), and on eventual interactions that may be established between the drugs and the lens material [ 22 ].…”

“…Drug-eluting IOLs have been recently proposed to pharmacologically hinder PCO. Celecoxib [ 32 ], erufosine [ 33 ], erlotinib [ 34 ], gefitinib [ 35 ], and methotrexate [ 36 ] were loaded with this purpose into IOLs by soaking in drug solutions. Despite the short-term release that is achieved with most of the investigated systems, a long-term effect on the proliferation of epithelial cells was registered with ex vivo canine models or human capsular bag models, suggesting the suitability of the method.…”

Research Progress Concerning a Novel Intraocular Lens for the Prevention of Posterior Capsular Opacification

“…In another study, drug-eluting IOLs loaded with the EGF inhibitors, gefitinib or erlotinib, could effectively slow LEC proliferation in ex vivo models of the human lens capsular bag. Additionally, sustainable drug release showed no toxicity to corneal endothelial cells [ 101 , 102 ].…”

Assessing the triad of biocompatibility, medical device functionality and biological safety

“…There are four potential targets for drug release; inhibition of LEC proliferation, hindering LEC migration, impeding EMT and clearing LECs. One example undergoing experimentation is the coating of IOLs with gefitnib, an epidermal growth factor receptor inhibitor, which can restrict LEC proliferation (Kassumeh, 2019); such drugs are quite powerful and their evaluation with respect to biological safety will have to be very comprehensive.…”