Multi-functional PHEMA-based Hydrogel Material For Corneal Contact Lens

Although the administration of eye drops is the most common way in the treatment of eye diseases,there are some disadvantages for this way,such as low drug bioavailability,high side effects and so on.In recent years,poly?2-hydroxyethyl methacrylate??p HEMA?-based hydrogel material with drug loading and slow delivery for corneal contact lens,has been widely concerned.However,there are some challenges for them as corneal contact lens.For example,tear proteins are prone to deposite on the surface of contact lens leading to the decrease of light transmittance and ocular inflammation caused by bacterial infection.Meanwhile,the hydrophilicity,oxygen permeability and sustained drug delivery of p HEMA-based contact lens materials need to be further improved.For that,in this thesis we developed a multi-functional p HEMA-based terpolymer hydrogel contact lens for eye diseases.In this system,2-hydroxyethyl methacrylate?HEMA?was the main matrix,and hydrophilic quaternary ammonium salt chitosan?HACC?with excellent antibacterial activity was introduced into the system by copolymerization so as to improve the surface hydrophilicity and reduce the tear protein adsorption of corneal contact lens.Meanwhile,the antibacterial activity of corneal contact lens was endowed to reduce ocular inflammation caused by bacterial infection.In addition,the derivative of?-cyclodextrin??-CD?was also copolymerized into the system for improving the loading capacity and sustained delivery of drugs.The investigations and results were as follows:?1?Acrylate modification of HACC and?-CD.Methacrylic anhydride?MA?-functionlized HACC?mHACC?with different substitution degrees of MA were prepared by changing the molar ratio of MA and HACC.¹H-NMR analysis confirmed that MA was successfully bonded to HACC.Firstly,mono-6-O-Ts-?-CD was synthesized by the monosubstitution reaction of4-toluene sulfonyl chloride?p-Tscl?with?-CD,and ¹H-NMR analysis confirmed the successful bonding of p-Tscl to?-CD.Secondly,amion-conjugated?-CD??-CD-HDA?was prepared by the reaction of mono-6-O-Ts-?-CD with 1,6-hexanediamine?HDA?,and ¹H-NMR analysis proved the successful conjugation of HDA to?-CD.Lastly,m CD with carbon-carbon double bond was synthesized through the ring-opening reaction of glycidyl methacrylate?GMA?with?-CD-HDA,and ¹H-NMR analysis confirmed that GMA was successfully bonded to?-CD-HDA.?2?Preparation and properties of p?HEMA-co-mHACC?hydrogels.The p?HEMA-co-mHACC?hydrogels with different MA substitution degrees and different mHACC contents were prapred by the copolymerization of mHACC as a macromolecular crosslinker and HEMA monomer,which was proved by FT-IR analysis.The compatibility between mHACC and p HEMA in the hydrogel was enhanced by increasing the MA substitution degree.While the MA substitution degree was 26%,p?HEMA-co-mHACC?hydrogels showed the optimal light transmittance and mechanical properties.The increase of m₂₆HACC content enhanced the surface hydrophilicity,oxygen permeability,surface electropositivity,lysozyme adsorption resistance and antibacterial activity of p(HEMA-co-m₂₆HACC)hydrogels.While the m₂₆HACC content was 5%,a light transmittance of over 92%,a tensile strength of 824 k Pa and an elongation at break of 169%,were achieved for p(HEMA-co-m₂₆HACC₅)hydrogel,which meets the requirements of GB11417.2-89for corneal contact lens materials in light transmittance and mechanical property.?3?Preparation and properties of p(HEMA-co-m₂₆HACC₅-co-m CD)hydrogels.Based on the optimal p(HEMA-co-m₂₆HACC₅)hydrogel prepared above,?-CD derivative?m CD?with drug loading and sustained delivery was introduced into the system.The p(HEMA-co-m₂₆HACC₅-co-m CD)hydrogels with different m CD contents were prepared by the copolymerization of of m CD,m₂₆HACC₅ and HEMA,which was confirmed by FT-IR analysis.The increase of m CD content not only enhanced the surface hydrophilicity,oxygen permeability,surface electropositivity,lysozyme and BSA adsorption resistance,and antibacterial activity of hydrogels,but also improved the loading capacity and sustained delivery of drugs.At a m CD content of 10%,the p(HEMA-co-m₂₆HACC₅-co-m CD₁₀)hydrogel showed a drug loading capacity of 14.7?g/mg and a drug delivery period of over 72 h.Meanwhile,a light transmittance of over 92%,a tensile strength of 832 k Pa and an elongation at break of116%,were achieved for this hydrogel,which meets the requirements of GB11417.2-89 for the corneal contact lens materials in the light transmittance and mechanical property.Therfore,p(HEMA-co-m₂₆HACC₅-co-m CD₁₀)hydrogel is a promising multifunctional contact lens material in the treatment of ophthalmic diseases.