Multifunctional Cerium Oxide Nanozyme for Synergistic Dry Eye Disease Therapy.

Dry eye disease (DED) is a chronic multifactorial ocular surface disease mainly caused by the instability of tear film, characterized by a series of ocular discomforts and even visual disorders. Oxidative stress has been recognized as an upstream factor in DED development. Diquafosol sodium (DQS) is an agonist of the P2Y2 receptor to restore the integrity/stability of the tear film. With the ability to alternate between Ce3+ and Ce4+, cerium oxide nanozymes could scavenge overexpressed reactive oxygen species (ROS). Hence, a DQS-loaded cerium oxide nanozyme was designed to boost the synergistic treatment of DED. Cerium oxide with branched polyethylenimine-graft-poly(ethylene glycol) as nucleating agent and dispersant was fabricated followed with DQS immobilization via a dynamic phenylborate ester bond, obtaining the DQS-loaded cerium oxide nanozyme (defined as Ce@PBD). Because of the ability to mimic the cascade processes of superoxide dismutase and catalase, Ce@PBD could scavenge excessive accumulated ROS, showing strong antioxidant and anti-inflammatory properties. Meanwhile, the P2Y2 receptors in the conjunctival cells could be stimulated by DQS in Ce@PBD, which can relieve the incompleteness and instability of the tear film. The animal experiments demonstrated that Ce@PBD significantly restored the defect of the corneal epithelium and increased the number of goblet cells, with the promotion of tear secretion, which was the best among commercial DQS ophthalmic solutions.

Multifunctional cerium oxide nanozymes with high ocular surface retention for dry eye disease treatment achieved by restoring redox balance.

Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. STATEMENT OF SIGNIFICANCE.

POSS and PEG Contained Copolymer for Antibioadhesive Rigid Contact Lenses Materials Application.

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

Refractive index adjustable intraocular lens design to achieve diopter control for improving the treatment of ametropia after cataract surgery.

Intraocular lens (IOL) implantation is currently the most effective clinical treatment for cataracts. Nevertheless, due to the growth of the eye axis in patients with congenital cataracts during the process of growth and development, the progressive incapacity of an IOL with a fixed focus does not meet the demands of practical usage, leading to the occurrence of ametropia. This work describes an innovative class of an IOL bulk material that offers good biosafety and light-controlled refractive index adjustment. Acrylate materials were synthesized for the preparation of IOLs by free radical polymerization of ethylene glycol phenyl ether methacrylate (EGPEMA), hydrophilic monomer 2-(2-ethoxyethoxy) ethyl acrylate (EA), and functional monomer hydroxymethyl coumarin methacrylate (CMA). Under 365/254 nm ultraviolet (UV) irradiation, the coumarin group could adjust the polymer material's refractive index through reversible photoinduced dimerization/depolymerization. Meanwhile, the potential for the IOL use is enabled by its satisfactory biosafety. Such a light-induced diopter adjustable IOL will be more appropriate for implantation during cataract surgery since it will not require the correction needed for ametropia and will offer more accurate and humane treatment. STATEMENT OF SIGNIFICANCE.

Photo-controllable drug releasing bulk polyacrylic intraocular lens material for safer posterior capsular opacification prevention.

Posterior capsular opacification (PCO) is the most common complication that occurs after intraocular lens (IOL) implantation in cataract therapy. In recent years, IOLs have been developed as drug delivery platforms, but concerns over the safety of uncontrolled proliferative drug release have arisen. Therefore, a controlled drug release strategy is needed for safer PCO prevention. In this study, a new monomer contained coumarin group was introduced in material preparation, and poly(ethylene glycol phenyl ether methacrylate-co-2-(2-ethoxyethoxy) ethyl acrylate-co-7-(2-methacryloyloxyethoxy)-4-methylcoumarin) (PEEC) acrylic IOL materials were synthesized. The antiproliferative drug 5-fluorouracil (5-FU) could be chemically grafted to the PEEC IOL materials easily via a light induced [2 + 2] cycloaddition reaction with the coumarin group, getting drug-loaded IOL (PEEC@5-FU IOL). The PEEC@5-FU IOL exhibited excellent optical and mechanical properties and biocompatibility. More importantly, the loaded 5-FU could be easily controlled from release by light irradiation via photo-dissociation of the cyclobutane ring that was obtained by the [2 + 2] cycloaddition reaction of 5-FU and coumarin. The in vitro and in vivo experiments demonstrated that such photo-controllable drug release IOL could effectively prevent PCO after implantation in a safe way.

Cascade reaction triggering and photothermal AuNPs@MIL MOFs doped intraocular lens for enhanced posterior capsular opacification prevention.

Posterior capsular opacification (PCO) is the most common complication after cataract surgery. Present strategies can't meet the clinical needs of long-term prevention. This research reports a novel intraocular lens (IOL) bulk material with high biocompatibility and synergistic therapy. Gold nanoparticles (AuNPs) doped MIL-101-NH2 metal-organic frameworks (MOFs) (AuNPs@MIL) was firstly fabricated via in situ reductions. Then the functionalized MOFs were uniformly mixed with glycidyl methacrylate (GMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA) to form the nanoparticle doped polymer (AuNPs@MIL-PGE), and which was used to fabricate IOL bulk materials. The materials' optical and mechanical properties with different mass contents of nanoparticles are investigated. Such bulk functionalized IOL material could efficiently remove residual human lens epithelial cells (HLECs) in the capsular bag in the short term, and can prevent PCO on demand in the long run by near-infrared illumination (NIR) action. In vivo and in vitro experiments demonstrate the biosafety of the material. The AuNPs@MIL-PGE exhibits excellent photothermal effects, which could inhibit cell proliferation under NIR and doesn't cause pathological effects on the surrounding tissues. Such functionalized IOL can not only avoid the side effects of the antiproliferative drugs but also realize the enhanced PCO prevention in clinical practice.

Correction: Design of foldable, responsively drug-eluting polyacrylic intraocular lens bulk materials for prevention of postoperative complications.

Correction for 'Design of foldable, responsively drug-eluting polyacrylic intraocular lens bulk materials for prevention of postoperative complications' by Yueze Hong et al., J. Mater. Chem. B, 2022, DOI: https://doi.org/10.1039/d2tb01974d.

Design of foldable, responsively drug-eluting polyacrylic intraocular lens bulk materials for prevention of postoperative complications.

Posterior capsular opacification (PCO), resulting from undesired intracapsular cell proliferation, is the most common complication of intraocular lens (IOL) implantation after cataract surgery. In recent years, IOLs have been developed into a drug delivery platform. Compared with traditional eye drops, drug-loaded IOLs have the characteristics of independent patient compliance and no other operation except surgical implantation. In this work, a series of poly(glycidyl methacrylate-co-2-(2-ethoxyethoxy)ethyl acrylate) (PGE) acrylic intraocular lens materials were synthesized as drug delivery platforms. The PGE synthesized with 10% crosslinking agent has excellent optical, foldable, and thermomechanical properties. An aldehyde group was subsequently introduced into the PGE chains, and an antiproliferative drug (doxorubicin) was immobilized onto the PGE chains via an H+-sensitive imine bond. The IOL exhibits H+-dependent Dox release behavior in a simulated pathological environment. The in vitro and in vivo systematical evaluations indicate that such a responsively drug-eluting PGE IOL can effectively prevent PCO.

Facile multifunctional IOL surface modification via poly(PEGMA-co-GMA) grafting for posterior capsular opacification inhibition.

Posterior capsule opacification (PCO) is a significant complication of intraocular lens (IOL) implantation in cataract surgery, in which the adhesion and proliferation of lens epithelial cells (LECs) on the implanted IOL surface play an important role. The surface modification of IOL to prevent LEC adhesion and proliferation is a practical way to reduce the incidence of PCO. In this study, a multifunctional binary copolymer of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA) was synthesized (poly(PEGMA-co-GMA), PPG) and chemically grafted onto the aminolyzed IOL surface, utilizing the coupling reaction of epoxy and amino groups. Doxorubicin (DOX) was subsequently immobilized on the surface coating via the reaction of epoxy and amino groups as well. Taking advantages of the hydrophilicity of the PEG segments in the copolymer coating and the anti-proliferative effects of the DOX, a multifunctional surface coating was easily established by the synthesized copolymer PPG. Such anti-proliferative drug immobilized hydrophilic coating modification may effectively reduce the cell adhesion and proliferation and thus it is hypothesized to have great potential in PCO inhibition. The synthesis of PPG was confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FTIR). The surface coating immobilization was demonstrated by X-ray photoelectron spectroscopy (XPS). The in vitro drug release profiles and the cell behaviors were also investigated to validate the multifunctional coating inhibition effect on cellular adhesion and antiproliferation. Finally, the in vivo ocular implantation was carried out on rabbit eyes to evaluate the effect of the coating modified IOL on the inhibition of postoperative PCO. It followed that such multifunctional coating modification can effectively inhibit the adhesion and proliferation of LECs and significantly reduce the incidence of PCO. All these results reveal that such PPG copolymer modification provides a facile yet effective way to inhibit PCO formation after IOL implantation.