Poly(2-hydroxyethyl methacrylate)/β-cyclodextrin-hyaluronan contact lens with tear protein adsorption resistance and sustained drug delivery for ophthalmic diseases.

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.