Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-04-24 , DOI: 10.1016/j.actbio.2020.04.002 Ruicong Li 1 , Xipeng Guan 2 , Xilin Lin 1 , Pengyue Guan 1 , Xiong Zhang 1 , Zhouquan Rao 1 , Lin Du 2 , Jiafeng Zhao 2 , Jianhua Rong 3 , Jianhao Zhao 3
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A series of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels containing cross-linked β-cyclodextrin-hyaluronan (β-CD-crHA), with tear protein adsorption resistance and sustained drug delivery, were developed as contact lens materials for eye diseases. β-CD-HA was synthesized from aminated β-CD and HA and then crosslinked within pHEMA hydrogel using polyethylenimine as a crosslinker. The synthesized β-CD-HA was characterized by 1H NMR analysis, and β-CD-crHA immobilized in pHEMA hydrogel was confirmed by FT-IR, SEM, and AFM analyses. The incorporation of β-CD-crHA significantly improved the surface hydrophilicity, water uptake ability, oxygen permeability, and flexibility of pHEMA hydrogel, but did not compromise light transmission. pHEMA/β-CD-crHA hydrogels not only decreased the tear protein adsorption because of the electrostatically mutual repulsion and the improved hydrophilicity, leading to the reduced adhesion of Staphylococcus aureus on the hydrogel surface, but also enhanced the encapsulation capacity and the sustainable delivery of diclofenac due to the formation of inclusion complexes between β-CD and drugs. All the hydrogels were nontoxic to 3T3 mouse fibroblasts by in vitro cell viability analysis. Among these hydrogels with different β-CD-crHA contents, pHEMA/β-CD-crHA10 hydrogel showed the lowest water contact angle of 52 °, the highest water content of 65%, the largest Dk value of 36.4 barrer, and the optimal modulus of 1.8 MPa, as well as a good light transmission of over 90%. The in vivo conjunctivitis treatment of rabbits for 72 h indicated that drug-loaded pHEMA/β-CD-crHA10 hydrogel presented a better therapeutic effect than both one dose administration of drug solution per day and drug-loaded pHEMA hydrogel. Thus, pHEMA/β-CD-crHA10 hydrogel is a promising contact lens material for ophthalmic diseases.
Statement of Significance
Topical eye drops are currently the most popular treatment for ophthalmic diseases, but frequent dosing is necessary to acquire the desirable clinical effect at the expense of systemic side-effects. Drug-loaded contact lenses, as an alternative of eye drops, possess many good performances and show potential applications. However, the sustained drug delivery and the tear protein adsorption resistance are still challenging for contact lenses. Hence, we developed a novel pHEMA/β-CD-crHA hydrogel by incorporating β-CD-crHA crosslinked network into pHEMA hydrogel. Besides the improvements in surface hydrophilicity, water uptake ability, oxygen permeability, and flexibility, pHEMA/β-CD-crHA hydrogel also reduced the adsorption of tear proteins and the adhesion of Staphylococcus aureus, enhanced the drug encapsulation, and prolonged the drug delivery, with better effect in the conjunctivitis treatment of rabbits. Thus, pHEMA/β-CD-crHA hydrogel is a potential contact lens material for treating ophthalmic diseases.
中文翻译：
聚（2-甲基丙烯酸羟乙基酯）/β-环糊精-透明质酸隐形眼镜，具有抗眼泪蛋白的吸附性和持续的药物递送能力，可用于眼科疾病。
开发了一系列含有交联β-环糊精-乙酰透明质酸（β -CD-crHA），具有抗泪液蛋白吸附性和持续药物递送功能的聚甲基丙烯酸2-羟乙酯（pHEMA）水凝胶，作为眼科疾病的隐形眼镜材料。β -CD-HA从胺化合成β -CD和HA，然后用聚乙烯亚胺作为交联剂的pHEMA水凝胶内交联。通过1 H NMR分析对合成的β -CD-HA进行表征，并通过FT-IR，SEM和AFM分析确定了固定在pHEMA水凝胶中的β -CD-crHA。β的掺入-CD-crHA可显着改善pHEMA水凝胶的表面亲水性，吸水能力，透氧性和柔韧性，但不影响透光率。pHEMA / β -CD-crHA水凝胶不仅由于静电互斥和改善的亲水性而降低了泪液蛋白的吸附，从而导致金黄色葡萄球菌在水凝胶表面上的粘附力降低，而且增强了胶囊的包封能力和可持续递送性。双氯芬酸是由于β -CD和药物之间形成了包合物。通过体外细胞生存力分析，所有水凝胶均对3T3小鼠成纤维细胞无毒。在这些具有不同β的水凝胶中-CD-crHA含量，pHEMA / β -CD-crHA 10水凝胶的最低水接触角为52°，最高水含量为65％，最大Dk值为36.4 barrer，最佳模量为1.8 MPa，以及超过90％的良好透光率。的体内结膜炎治疗兔72小时的表明装载药物的pHEMA / β -CD-CRHA 10水凝胶呈现比每天和载有药物的水凝胶的pHEMA药物溶液既一个剂量给药更好的治疗效果。因此，pHEMA / β -CD-crHA 10水凝胶是用于眼科疾病的有前途的隐形眼镜材料。
重要声明
当前，局部滴眼剂是用于眼科疾病的最流行的治疗方法，但是为了获得理想的临床效果而需要频繁给药以牺牲全身性副作用为代价。载药隐形眼镜作为滴眼剂的替代品，具有许多良好的性能，并显示出潜在的应用前景。然而，对于隐形眼镜而言，持续的药物输送和泪液蛋白的吸收阻力仍然是挑战。因此，我们通过将β -CD-crHA交联网络结合到pHEMA水凝胶中，开发了一种新型的pHEMA / β -CD-crHA水凝胶。除了改善表面亲水性，吸水能力，透氧性和柔韧性外，pHEMA / β -CD-crHA水凝胶还减少了眼泪蛋白的吸附和黏附性。金黄色葡萄球菌，增强了药物的包封性，并延长了药物的递送，对兔结膜炎的治疗效果更好。因此，pHEMA / β -CD-crHA水凝胶是用于治疗眼科疾病的潜在隐形眼镜材料。
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