In vivo study on the performance of therapeutic intraocular lens loaded with an antibiotic and an anti-inflammatory

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

Bottom-Up Fabrication of PEG Brush on Poly(dimethylsiloxane) for Antifouling Surface Construction

Poly(dimethylsiloxane) silicones have found many applications in biomedical devices, whereas their surface hydrophobicity always brings about unexpected bioadhesion, causing complications of the implanted biomedical devices. In this work, surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization was utilized to generate PEG brushes on silicone surface, obtaining highly hydrophilic surface coatings. Such PEG brush coated silicone presents excellent antifouling to protein, cells, and bacteria, which may have great potential in implantable biomaterial surface modifications

Dual drug delivery from hydrophobic and hydrophilic intraocular lenses: in-vitro and in-vivo studies

Posterior capsule opacification (PCO) still remains the most frequent long term complication after cataract surgery, while endophthalmitis is rare but severe and should be prevented at all cost. Intraocular lenses (IOLs) with different designs (eg. edge and body-haptics angle) and materials (acrylic hydrophobic and acrylic hydrophilic surfaces) have been studied to reduce PCO. For the prevention of endophthalmitis, intracameral injection followed or not by topical treatment with antibiotics and anti-inflammatories are usually prescribed. The objective of this work was to investigate the use of IOLs as controlled release platforms of two drugs, the antibiotic moxifloxacin (MXF) and the anti-inflammatory ketorolac (KTL) that could advantageously substitute the usual treatment. Two types of IOLs were chosen, hydrophobic and hydrophilic. Hydrophobic IOLs have shown better results in the prevention of PCO because they adhere better to the posterior capsular bag, while hydrophilic IOLs are advised in the case of patients with uveitis, glaucoma or diabetes. The IOLs were loaded with MXF + KTL and sterilized by high hydrostatic pressure. Both IOLs reduced the tendency for adhesion of LECs. In vivo tests were done to compare the concentration of the drugs in the aqueous humor obtained after eye drops administration and drug-loaded IOLs implantation. The developed IOLs were able to release MXF and KTL at therapeutic levels, in a sustained way, which contrasts with the eye drops prophylaxis. No PCO signs were detected and histological analyses demonstrated biocompatibility of these devices.publishe

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

Abstract 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

A bio-inspired, one-step but versatile coating onto various substrates with strong antibacterial and enhanced osteogenesis

It is of great interest to prepare osteogenic and antibacterial coatings for successful implants. Current coating techniques suffer from being time-consuming, substrate material or shape dependence, expensive equipment, environmental pollution, low stability, processes that are difficult to control, etc. Herein, inspired by mussels, we report a one-step and versatile method to fabricate a dual functional coating. The coating is finished in minutes independently of materials or dimensions of substrates. Thus, our coatings exhibit strong antibacterial ability against both Gram-positive bacteria S. aureus, and Gram-negative bacteria E. coli, support the proliferation of dental pulp stem cells (DPSCs), and are powerful for inducing osteogenic differentiation. The universality, facility, rapidness, and mildness of our coating process, which is also environmentally-friendly and cost-effective, points towards potential applications in bone or dental implants

Simulation and Analysis of Wind Pressure Coefficient of Landslide-Type Long-Span Roof Structure

This article carries out a numerical simulation of a landslide-type long-span roof structure, Harbin Wanda Cultural Industry Complex. The maximum span of the landslide-type roof is 150 m and the minimum span is 90 m, with a minimum height of 40 m and a maximum height of 120 m, and the roof area is divided into three different parts. The large eddy simulation (LES) method is used to simulate and record the wind pressure coefficient of the roof. The distribution law and cause of the mean wind pressure coefficient of the roof are firstly analyzed, and the comparison with the existing wind tunnel test data proves the validity of the numerical simulation. Secondly, a qualitative analysis is made on the distribution of root mean square (RMS) fluctuating coefficients. Subsequently, the non-Gaussian characteristics of the roof are briefly discussed, and the peak factor distribution is calculated. Finally, based on the total wind pressure coefficient, a simple evaluation method for judging favorable and unfavorable wind direction angles is proposed, and only the shape of the roof and wind angle need to be known

NIR-triggered thermosensitive polymer brush coating modified intraocular lens for smart prevention of posterior capsular opacification

Abstract Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment

Multifunctional Polymer Vesicles for Synergistic Antibiotic–Antioxidant Treatment of Bacterial Keratitis

As an acute ophthalmic infection, bacterial keratitis (BK) can lead to severe visual morbidity, such as corneal perforation, intraocular infection, and permanent corneal opacity, if rapid and effective treatments are not available. In addition to eradicating pathogenic bacteria, protecting corneal tissue from oxidative damage and promoting wound healing by relieving inflammation are equally critical for the efficient treatment of BK. Besides, it is very necessary to improve the bioavailability of drugs by enhancing the ocular surface adhesion and corneal permeability. In this investigation, therefore, a synergistic antibiotic–antioxidant treatment of BK was achieved based on multifunctional block copolymer vesicles, within which ciprofloxacin (CIP) was simultaneously encapsulated during the self-assembly. Due to the phenylboronic acid residues in the corona layer, these vesicles exhibited enhanced muco-adhesion, deep corneal epithelial penetration, and bacteria-targeting, which facilitated the drug delivery to corneal bacterial infection sites. Additionally, the abundant thioether moieties in the hydrophobic membrane enabled the vesicles to both have ROS-scavenging capacity and accelerated CIP release at the inflammatory corneal tissue. In vivo experiments on a mice model demonstrated that the multifunctional polymer vesicles achieved efficient treatment of BK, owing to the enhanced corneal adhesion and penetration, bacteria targeting, ROS-triggered CIP release, and the combined antioxidant–antibiotic therapy. This synergistic strategy holds great potential in the treatment of BK and other diseases associated with bacterial infections