Liu Xiaoqi, Chen Jiang, Qu Chao, Bo Gong, Jiang Lang, Zhao Hui, Zhang Jing, Lin Yin, Hua Yu, Yang Ping, Huang Nan, Yang Zhenglin
Institute of Biomaterials and Surface Engineering, Key Lab for Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, No. 111 of the North First Section of Second Ring Road, Chengdu, CN 610031, China.
Sichuan Key Laboratory for Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32 of the West Second Section of First Ring Road, Chengdu, CN 610072, China.
ACS Biomater Sci Eng. 2018 May 14;4(5):1568-1579. doi: 10.1021/acsbiomaterials.7b00977. Epub 2018 Apr 4.
The use of contact lenses for the early treatment of bacterial or fungal keratitis has become a new research focus. Two main requirements of the therapeutic contact lenses are antimicrobial ability and visible light transmittance. Silver nanoparticles (AgNPs), as a nonspecific antimicrobial component, have been loaded onto contact lenses for the treatment of bacterial and fungal keratitis. Recently, it was reported that, via a simple immersion method, AgNPs can be synthesized and fixed onto the surface of polydopamine (PDA)-coated materials. However, in this study, we found that the above traditional method has the disadvantages of poor AgNP loading and low visible light transmittance, which could be induced by a limited amount of phenolic hydroxyl groups on and second oxidation of the PDA coating, respectively. To overcome these disadvantages, in this paper, we provided a facile and novel method to robustly bind multilayer-AgNPs on contact lens surfaces by using dopamine as a reducing agent and bioglue. In comparing with the monolayer-AgNP-loaded contact lenses fabricated by the traditional method, the multilayer-AgNP-loaded contact lenses had excellent antimicrobial ability and better visible light transmittance. Moreover, the multilayer-AgNP-loaded contact lens had low cytotoxicity to human corneal epithelial cells and anti-inflammation properties. Furthermore, the shortcoming of decreasing visible light transmittance induced by excess adherence of AgNPs on the multilayer-AgNP-loaded contact lens was alleviated by decreasing the size of AgNPs through altering the concentration of dopamine and AgNO. Contact lenses loaded with small AgNPs (Ag@PDA-2.5, diameter ≈ 25-50 nm) had approximately the same Ag release and antimicrobial abilities, but significantly better visible light transmittance and anti-inflammatory properties than the contact lenses loaded with large AgNPs (Ag@PDA-5, diameter ≈ 50-75 nm). After that, testing indicated the promising therapeutic strategy of multilayer-AgNP-loaded contact lenses (Ag@PDA-2.5) for early bacterial keratitis and fungal keratitis. In addition, PDA coating could provide reactive sites to immobilize other biomolecules or drugs on this multilayer-AgNP-loaded contact lens for further combination therapies in treating bacterial or fungal keratitis. Finally, the stability of the visible light transmittance of the multilayer-AgNP-loaded contact lens was detected. The visible light transmittance of Ag@PDA-2.5 was weakened after being cultured with an extremely high concentration of bacteria, while it was stable in the moderate work environment. Though PDA coating had been wildly used to modify implantation devices, however, few studies about PDA coating modified contact lenses have been reported so far. Therefore, this research also provides an important basis for using PDA coating to modify a therapeutic contact lens.
使用隐形眼镜对细菌性或真菌性角膜炎进行早期治疗已成为新的研究热点。治疗性隐形眼镜的两个主要要求是抗菌能力和可见光透过率。银纳米颗粒（AgNPs）作为一种非特异性抗菌成分，已被加载到隐形眼镜上用于治疗细菌性和真菌性角膜炎。最近有报道称，通过一种简单的浸渍方法，可以合成AgNPs并将其固定在聚多巴胺（PDA）涂层材料的表面。然而，在本研究中，我们发现上述传统方法存在AgNP负载量低和可见光透过率低的缺点，这分别是由PDA涂层上有限数量的酚羟基和PDA涂层的二次氧化引起的。为克服这些缺点，在本文中，我们提供了一种简便新颖的方法，通过使用多巴胺作为还原剂和生物胶水，将多层AgNPs牢固地结合在隐形眼镜表面。与传统方法制备的单层负载AgNP的隐形眼镜相比，多层负载AgNP的隐形眼镜具有优异的抗菌能力和更好的可见光透过率。此外，多层负载AgNP的隐形眼镜对人角膜上皮细胞具有低细胞毒性和抗炎特性。此外，通过改变多巴胺和硝酸银的浓度来减小AgNPs的尺寸，缓解了多层负载AgNP的隐形眼镜上由于AgNPs过度附着而导致可见光透过率降低的缺点。负载小尺寸AgNPs（Ag@PDA - 2.5，直径≈25 - 50 nm）的隐形眼镜具有大致相同的银释放量和抗菌能力，但与负载大尺寸AgNPs（Ag@PDA - 5，直径≈50 - 75 nm）的隐形眼镜相比，其可见光透过率和抗炎特性明显更好。之后，测试表明多层负载AgNP的隐形眼镜（Ag@PDA - 2.5）对早期细菌性角膜炎和真菌性角膜炎具有有前景的治疗策略。此外，PDA涂层可为将其他生物分子或药物固定在这种多层负载AgNP的隐形眼镜上提供反应位点，用于治疗细菌性或真菌性角膜炎的进一步联合治疗。最后，检测了多层负载AgNP的隐形眼镜可见光透过率的稳定性。Ag@PDA - 2.5在与极高浓度细菌培养后可见光透过率减弱，而在适度的工作环境中则保持稳定。尽管PDA涂层已被广泛用于修饰植入装置，然而，迄今为止关于PDA涂层修饰隐形眼镜的研究报道很少。因此，本研究也为使用PDA涂层修饰治疗性隐形眼镜提供了重要依据。
