Introduction: Cataract is a serious eye condition affecting millions of people worldwide. Although the implantation of intraocular lens (IOL) can be routinely performed, the post-cataract surgery-related inflammation and posterior capsule opacification are common symptoms. To address these drawbacks, this study aims to develop a novel drug-eluting IOL that can effectively exhibit anti-cell adhesion and anti-inflammatory activities. Materials and Methods: The IOL samples (IOL-C group) were pre-treated with oxygen plasma (IOL-OP group) and modified with hetero-bifunctional poly(ethylene glycol) (PEG) derivatives (IOL-PEG group). After conjugation with matrix metalloproteinase (MMP)-sensitive peptide, the IOLs were further loaded with the drug amfenac (IOL-AF) by carbodiimide coupling reaction. Surface characterizations and biocompatibility assessments were performed. Then, the protein adsorbed amount, cell adhesion ratio, and drug release profile were also determined. In a rabbit model of experimental cataract, the therapeutic efficacy of drug-eluting IOL was evaluated. All animal procedures were approved by the Institutional Review Board and were carried out in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Results and Discussion: FTIR, ESCA, AFM, and water contact angle studies indicated that surface modification of functionalized IOLs can be successfully achieved. Light transmittance measurements demonstrated that the surface functionalization with PEG does not alter the optical properties of IOL materials. In vitro and in vivo studies showed that the functionalized IOLs are biocompatible towards lens epithelial cell cultures and anterior segment tissues. However, changes in anti-protein adsorption and anti-cell adhesion appear to be significant on IOL-PEG, suggesting crucial role of PEG molecules on the IOL surfaces. Our results show a programmable release of drug from the samples of IOL-AF groups. In addition, studies on degree of oxidative stress and inflammation level indicate a significant decrease in the generation of ROS, intracellular calcium level, COX-2 activity, and PGE2 level in IOL-AF groups. Results of animal tests further confirmed the pharmacological action of the amfenac released from the functionalized IOLs. Slit-lamp examinations, IOP measurements, and immunohistochemistry demonstrate the limited inflammation after 28 days of surgical insertion of drug-eluting IOL implants. Conclusion: The present study suggests that the drug-eluting IOLs are more effective and beneficial than traditional postoperative treatments with the possibility to last for up to 28 days. The biomaterial-functionalized IOLs may hold promise to address common post-cataract surgical complications.
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