Matrix metalloproteinase-2 and pH-responsive drug eluting multilayer as intraocular lens coating to improve the posterior capsule opacification inhibition

Intraocular lens (IOL) is a crucial implant for cataract therapy. Posterior capsule opacification (PCO) is the most common postoperative complication after IOL implantation, which is the abnormal hyperplasia of the residual lens epithelial cells (LECS) after IOL implantation in cataract surgery. It is reported that the cellular microenvironment in the lens capsule changes after surgery, such as the elevated secretion of Matrix metalloproteinases (MMPs) and a decrease in pH due to undesired cell proliferation. In this study, MMP-2 and pH-triggered drug delivery polysaccharide multilayer coating was designed and introduced onto the IOL surface for obtaining the cellular microenvironment-sensitive drug-eluting intraocular implant. The methacrylated heparin (HEP-MA) was synthesized and used to layer-by-layer self-assemble with the doxorubicin-loaded chitosan nanoparticles on the IOL surface. The Matrix metalloproteinase-2 (MMP-2) sensitive peptide with Cysteine contained in both ends (GCRD-GPQGIWGQ-DRCG) was then used to crosslink the polysaccharide multilayer via the Michael addition reaction between sulfhydryl group in Cysteines and double bonds in methacrylate groups. The multilayer construction and subsequent cross-linking were validated through Ultraviolet-visible spectrophotometer (UV-Vis) and Fourier-transform infrared spectroscopy (FTIR). After modification, the IOL material surface becomes more hydrophilic while the optical properties were well maintained. The MMP-2 and pH-sensitive drug sustained release coating were successfully obtained on the IOL surface via such design. The enzyme-triggered cell proliferation inhibition was realized in the in vitro experiments. In an animal model, significant upregulation of MMP-2 was observed in the aqueous humor after cataract surgery. The multi-functionalized polysaccharide-coated IOL implanted in the animal eye via cataract surgery effectively inhibits PCO formation while it keeps good in-vivo biosafety.