Hydrogels For Corneal Contact Lenses With Sustained Drug Delivery And Tear Protein Adsorption Resistance

There are some challenges in the current treatment of eye diseases, such as low drug availability for eye drops, and prone to adsorb tear protein and induce bacterial infection for longly wearing corneal contact lens. For that, a sort of hydrogel with sustainable drug delivery and tear propein adsorption resistance was fabricated as a candidate material for therapeutic contact lens. Firstly, β-cyclodextrin-conjugated hyaluronan(β-CD-HA) was synthesized by the reaction of amino activated β-cyclodextrin(β-CD) and hyaluronan(HA) in the presence of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride / N-Hydroxysuccinimide(EDC/NHS). Then, β-CD-HA was cross-linked within the poly(2-hydroxyethyl methacrylate)(pHEMA) hydrogel by polyethylene(PEI) as the crosslinking agent, so as to form a pHEMA/β-CD-HA hybrid hydrogel with an interpenetrating polymer network. A series of characterizations, including proton nuclear magnetic resonance spectroscopy(1H NMR), Fourier transform infrared spectroscopy(FT-IR), scanning electron microscopy(SEM), atomic force microscopy(AFM), and water contact angle measurement, water absorption test, mechanical tensile test, light transmittance test, tear protein adsorption test, bacterial adhesion test, diclofenac loading and delivery, and cell viability, were performed to investigate the effect of β-CD-HA content on the morphology, water absorption, mechanical property, light transmission, tear protein adsorption resistance, bacterial adhesion resistance, drug loading capacity and sustained delivery, and cytotoxicity of pHEMA/β-CD-HA hybrid hydrogel.1H NMR analysis showed that β-CD was successfully bonded to HA with a substitution degree of 18.2%, and FT-IR analysis also implied the presence of cross-linked β-CD-HA within p HEMA hydrogel due to the increasing peak intensity of amide groups. SEM and AFM results showed that after the incorporation of β-CD-HA cross-linked network into pHEMA hydrogel, the hydrogel surface became rougher with the increase of β-CD-HA content.Water contact angle test results showed that in comparison to pHEMA hydrogel, pHEMA/β-CD-HA hybrid hydrogel exhibited a greatly improved hydrophilicity with a decreasing water contact angle from 91° to approximate 50° with increasing the β-CD-HA content. Among them, pHEMA/β-CD-HA-10 hydrogle presented the lowest water contact angle of 52°. The water adsorption test results showed that with the increase of β-CD-HA amount, pHEMA/β-CD-HA hydrogel enhanced the water absorption from 51.3% to 64.8%.The tensile test results showed that with the increase of β-CD-HA amount, the tensile strength at break of the hydrogel decreased from 3.5 MPa to 2.3 MPa, the tensile modulus decreased from 4.7 MPa to 2.3 MPa, while the elongation at break increased from 230% to 470%, indicating that the introduction of β-CD-HA cross-linked network into pHEMA hydrogel reduced the tensile strength at break and tensile modulus, but increased the rupture enlongation making it tougher.The light transmittance test results show that the introduction of β-CD-HA cross-linked network did not significantly decrease the light transmission of the hydrogel, and all hdyrogels presented a light transmittance of over 90.0%. Tear protein adsorption experimental results show that the incorporation of β-CD-HA remarkly reduced the tear protein adsorption, including lysozyme, albumin, β-lactoglobulin and lgG proteins. The more amount of β-CD-HA in pHEMA hydrogel, the lower tear protein adsorption, moreover pHEMA/β-CD-HA-10 hydrogel showed a superior tear protein adsorption resistance to the commercial contact lense “Binfen” of BAUSCH LOMB brand.Staphylococcus aureus adhesion test results showed that the introduction of β-CD-HA effectively reduced the bacterial adhesion, indicative of a certain anti-microbial effect, moreover pHEMA/β-CD-HA-10 hydrogel showed a better anti-microbial property than “Binfen” of BAUSCH LOMB brand. The diclofenac loading and delivery results showed that the presence of β-CD-HA in pHEMA hydrogel significantly increased drug loading capacity from 17.6mg/g for pHEMA hydrogel to 35.2mg/g for pHEMA/β-CD-HA-10 hydrogel that was much higher than “Binfen”(13mg/g) of BAUSCH LOMB. Additionally, pHEMA/β-CD-HA hydrogel also distinctly slowed down the delivery of diclofenac as well. Within 24 hours, the diclofenac accumulative release percentage of 91% was obtained for pHEMA hydrogel similar to “Binfen” of of BAUSCH LOMB, as opposed to less than 30% for all pHEMA/β-CD-HA hydrogels indicative of their advantage in drug sustained delivery.In summary, pHEMA/β-CD-HA hybrid hydrogel can not only improve the hydrophilicity and fracture toughness of hydrogel, effectively reduce the tear protein adsorption and bacterial adhesion, but also enhance the loading capacity and drug sustained delivery of drugs, which is a promising corneal contact len material in eye disease therapy.