PMID- 32339710 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210514 IS - 1878-7568 (Electronic) IS - 1742-7061 (Linking) VI - 110 DP - 2020 Jul 1 TI - Poly(2-hydroxyethyl methacrylate)/beta-cyclodextrin-hyaluronan contact lens with tear protein adsorption resistance and sustained drug delivery for ophthalmic diseases. PG - 105-118 LID - S1742-7061(20)30199-9 [pii] LID - 10.1016/j.actbio.2020.04.002 [doi] AB - A series of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels containing cross-linked beta-cyclodextrin-hyaluronan (beta-CD-crHA), with tear protein adsorption resistance and sustained drug delivery, were developed as contact lens materials for eye diseases. beta-CD-HA was synthesized from aminated beta-CD and HA and then crosslinked within pHEMA hydrogel using polyethylenimine as a crosslinker. The synthesized beta-CD-HA was characterized by (1)H NMR analysis, and beta-CD-crHA immobilized in pHEMA hydrogel was confirmed by FT-IR, SEM, and AFM analyses. The incorporation of beta-CD-crHA significantly improved the surface hydrophilicity, water uptake ability, oxygen permeability, and flexibility of pHEMA hydrogel, but did not compromise light transmission. pHEMA/beta-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 beta-CD and drugs. All the hydrogels were nontoxic to 3T3 mouse fibroblasts by in vitro cell viability analysis. Among these hydrogels with different beta-CD-crHA contents, pHEMA/beta-CD-crHA(10) hydrogel showed the lowest water contact angle of 52 degrees , 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/beta-CD-crHA(10) hydrogel presented a better therapeutic effect than both one dose administration of drug solution per day and drug-loaded pHEMA hydrogel. Thus, pHEMA/beta-CD-crHA(10) 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/beta-CD-crHA hydrogel by incorporating beta-CD-crHA crosslinked network into pHEMA hydrogel. Besides the improvements in surface hydrophilicity, water uptake ability, oxygen permeability, and flexibility, pHEMA/beta-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/beta-CD-crHA hydrogel is a potential contact lens material for treating ophthalmic diseases. CI - Copyright (c) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - Li, Ruicong AU - Li R AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. FAU - Guan, Xipeng AU - Guan X AD - Guangzhou Yuexin Biomedical Technology Co., Ltd, Guangzhou 510001, China. FAU - Lin, Xilin AU - Lin X AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. FAU - Guan, Pengyue AU - Guan P AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. FAU - Zhang, Xiong AU - Zhang X AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. FAU - Rao, Zhouquan AU - Rao Z AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. FAU - Du, Lin AU - Du L AD - Guangzhou Yuexin Biomedical Technology Co., Ltd, Guangzhou 510001, China. FAU - Zhao, Jiafeng AU - Zhao J AD - Guangzhou Yuexin Biomedical Technology Co., Ltd, Guangzhou 510001, China. FAU - Rong, Jianhua AU - Rong J AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China. FAU - Zhao, Jianhao AU - Zhao J AD - Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China. Electronic address: jhzhao@jnu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200424 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - 0 (Eye Proteins) RN - 0 (Hydrogels) RN - 0 (Methacrylates) RN - 0 (beta-Cyclodextrins) RN - 0 (tear proteins) RN - 25249-16-5 (Polyhydroxyethyl Methacrylate) RN - 6E1I4IV47V (hydroxyethyl methacrylate) RN - 9004-61-9 (Hyaluronic Acid) SB - IM MH - Adsorption MH - Animals MH - *Contact Lenses MH - *Eye Diseases MH - Eye Proteins MH - Hyaluronic Acid MH - Hydrogels/pharmacology MH - Methacrylates MH - Mice MH - Polyhydroxyethyl Methacrylate MH - Rabbits MH - Spectroscopy, Fourier Transform Infrared MH - *beta-Cyclodextrins OTO - NOTNLM OT - Contact lens OT - Drug delivery OT - Ophthalmic disease OT - Poly(2-hydroxyethyl methacrylate) OT - Tear protein adsorption OT - beta-cyclodextrin-hyaluronan COIS- Declaration of Competing Interest The authors declare no conflict of interest. EDAT- 2020/04/28 06:00 MHDA- 2021/05/15 06:00 CRDT- 2020/04/28 06:00 PHST- 2019/12/31 00:00 [received] PHST- 2020/03/18 00:00 [revised] PHST- 2020/04/02 00:00 [accepted] PHST- 2020/04/28 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/04/28 06:00 [entrez] AID - S1742-7061(20)30199-9 [pii] AID - 10.1016/j.actbio.2020.04.002 [doi] PST - ppublish SO - Acta Biomater. 2020 Jul 1;110:105-118. doi: 10.1016/j.actbio.2020.04.002. Epub 2020 Apr 24.