Preparation Of TiO₂/PMMA IOL And Its Safety Evaluation By Animal Experiments

Purpose:To prepare intraocular lens with good biocompatibility by nano-TiO2 films surface modified on polymetylmethacrylate(PMMA) intraocular lens, test its safety evaluation by animal experiments in order to provide theoretical basis for clinical applications and relevant experiment in the future.Methods: Prepare TiO2 films on PMMA substrate with the aid of air plasma treatment to produce a more hydrophilic surface on the PMMA, followed by dip-coating of TiO2 in a TiO2 sol. Scan the surface with scanning electron microscope to observe the surface shape modified by nano-TiO2 film,then test its animal safety evaluation. (1)Acute toxicity test: After injection of The TiO2/PMMA intraocular lens extracts into mice, observe the appearance of the animals in 72h. (2)Sub-acute toxicity test: implante TiO2/PMMA intraocular lens into mice, 2 weeks after count of hemoglobin, red blood cells, white blood cells, 8 weeks after taking heart, liver, lung, conventional biopsy, HE stain, microscopic examination. (3)Sensitization experiment: with saline water and 2% 2,4 - dinitrofluorobenzene (DNFB) solution of acetone for contrast, use skin reaction classification scoring system to score,observed whether TiO2/PMMA intraocular lens extracts role in sensibilization or not. (4)Hemolysis test: to make the control of normal saline and distilled water, measuring the absorbance of the control solution to calculate the rate of hemolysis. (5)Micronucleus test: with normal saline and cyclophosphamide compared,observed micro-nucleated cells of polychromatic erythrocytes of mouse after administration.(6)Subcutaneous implantation test: with TiO2/PMMA intraocular lens implantation in New Zealand white rabbits subcutaneously, in 2weeks, 4weeks, 8weeks, 12weeks animals were killed to remove the surrounding tissue and intraocular lens, cut soft tissue, conventional slice, HE stain, microscopic examination.(7)Pyrogen test: inject TiO2/PMMA intraocular lens extracts into the New Zealand white rabbits from ear marginal, observe whether there was significantly increased of body temperature. (8)Extracts toxicity: inject TiO2/PMMA intraocular lens extracts into anterior chamber of the New Zealand white rabbits, killed the animal after 8 weeks, removed the eyeball, cut anterior segment organize, conventional slice, HE stain, microscopic examination.Results: The surface of nano-TiO2 film surface modified PMMA intraocular lens is uniform formation, Animal safety evaluation results show:(1) Acute toxicity test: after injection of The TiO2/PMMA intraocular lens extracts into mice, find out the mice without toxic reaction;(2)Sub-acute toxicity test: with TiO2/PMMA intraocular lens implant into mice, general condition of animals remained norma1.Weight, hemoglobin, red blood cell count and white blood cell count of experimental animals altered slightly after two weeks.There is no significant pathological change after the examination of the organs after 8 weeks. (3)Sensitization experiment: TiO2/PMMA intraocular lens extraction role in non-sensitized; (4)Hemolytic rate : the hemolytic rate of The TiO2/PMMA intraocular lens extracts were 2.87% ,which met the requirement of hemolysis test standards a medical materia1. (5)Micronucleus test: there is significant difference between the experimental group and the cyclophosphamide positive control group, there is no significant difference between the negative saline control group and the experimental group,micronucleus rate of the experimental group is less than 5‰of the International Pharmacopoeia standards for positive, which have non-mutagenic response;(6)Subcutaneous implantation test: it revealed that implantation did not cause any local redness.There were little inflammatory cell infiltrations around the material 12weeks after implantation.(7) Pyrogen test: by injecting the TiO2/PMMA intraocular lens extracts in rabbits found a raise in the body Temperature less than 0.6℃,with total increase less than 1.4℃,to meet the accepted criteria for the pyrogen test.(8)Extracts toxicity: the pathological section of anterior segment, such as cornea, iris, ciliary body, look virtually the same as the control group 8weeks after injection, suggesting TiO2/PMMA intraocular lens extracts has no toxic effect.Conclusions: TiO2/PMMA intraocular lens have good biocompatibility.