Preparation And Evaluation Of The 5-Fluorouracil Loaded Membrane Based On Chitosan For Glaucoma Filtering Surgery

Objective:The fibroplasia and cicatrization after the glaucoma filtering surgery isthe main reason leading to failure.Clinically,two methods were used for reducingcicatrization.One is to use drugs to inhibit cicatrization,which also causescomplication;the other is to apply the implantation,which can physically isolatesubconjunctival space.But the implantation doesn't get the anti-fibrosis effect,and itsapplication also be limited by the immunological rejection,source and other factors.Thus,one focus of the glaucoma filtering surgery is the improvement of theimplantation,selecting the biomacromolecule which got good biocompatibility,slowly biodegradability and anti-fibrosis effect,and loading anti-fibrosis drugs withthe implantation for inhibiting cicatrization.Chitosan is been widely researched andapplied in medical and biomaterial fields due to its superordinary bionomics.Thepurpose of this experiment is to prepare and research the 5-Fluorouracil loadedmembrane based on chitosan,evaluating the anti-fibrosis effect on glaucoma filteringsurgery.Methods:1.Prepare and purify hydroxypropylated chitosan (Hp-CTS).Evaluatethe properties of the Hp-CTS systematically.2.Chemically modify 5-Fluorouracilfor 5-Fluorouracil-1- acetic acid(5-Fu-ac).3.Three membranes with different 5-Fuloadings are prepared by covalent cross-linking through carbodiimide,betweenHp-CTS and 5-Fu-ac with different dosage.Their physico-chemical properties,drugdelayed release ability,cell attachment,biodegradability,biocompatibility and otherproperties were evaluated.4.Evaluate the anti-fibrosis effect of 5-Fu loadedmembrane in the rabbit glaucoma filtering surgery by estimating the variation of theintraocular pressure (IOP) and the filtering bleb. Results:1.Hp-CTS prepared and purified are aseptic and consistent with thestandard of medical use.Hp-CTS got favorable biodegradability and biocompatibility.And the high concentration of Hp-CTS had significant inhibition effect on the L-929fibroblast.2.The technology for preparing the 5-Fu loaded membrane through thecovalent cross-linking between Hp-CTS and 5-Fu-ac was designed.The 5-Fu loadedmembranes could delay the release of drug in different extent.The membranes got thesuitable physico-chemical properties.3.The membranes had different extentinhibition effect on the L-929 and subconjunctival fibroblast in vitro,and the moredrug loaded the more obvious of the inhibition effect.The membranes were alsoproved to have good biocompatibility and slow biodegradability in the rats'subcutaneous tissue and muscle tissue.4.In the rabbit glaucoma filtering surgery,the5-Fu loaded membrane did better in reducing intraocular pressure and prolonging thesurvival time of filtering bleb than control group and 0# membrane.The resultIndicated that the 5-Fu loaded membrane got some extent effect of prolonging thesurvival time of the bleb and reducing intraocular presser.Conclusions:In this experiment,the 5-Fu loaded Hp-CTS membranes got the suitablephysico-chemical properties,drug delayed releasing ability,inhibited the fibroblastability in vitro,good biocompatibility and biodegradability。In the rabbit glaucomafiltering surgery,the 5-Fu loaded membrane got effect reducing intraocular presser insome extent.