DEVELOPMENT OF HYDROGEL AS VITREOUS SUBSTITUTE

Abstract

Vitreousisatransparenthydrogelplacedbetweenthelensandtheretinaof an eye.Ithelpsinmaintainingtheroundshapeoftheeyeandabsorbsmechanical shocks totheheadoreye,bymaintainingproperintraocularpressure(IOP);aidsin clear visionandtransportnutrientswithintheeye. The vitreouspresentinoureye,isliquefied/damagedduetoaging,excessive exposuretolight,oxidativedamage,increasedproteolyticactivity,andtrauma. Vitreousdamagecancauseblurredvision,reducedperipheralvision,andthesudden appearance ofalargenumberoffloaters;ifnottreatedinduetime,therewillberetinal detachment whichwillcausepermanentvisionloss.Vitreousisnotself-generatedor replenished: that’swhy,thereisaneedtofillthevitreouscavitywithasuitable artificial vitreoussubstitute(AVS)formaintainingthenormalfunctionofthenatural vitreous. Silicone oilandfluorinatedgasesareusedasAVSorclinicaltamponades, buttheiruseislimitedduetotheirtoxicityandsomecomplications.Alotofpolymer based materials,byvariousscientists,havebeentestedandproposedasvitreous implants. Butallareassociatedwithseveraladvantagesanddisadvantages,andthere is noidealAVStilldate.Thus,developinganidealvitreoussubstitute/implantisa current challenge. Another problemwithAVS:whileinjecting/implantingthevitreous substitutes insidethevitreouschamber,therearechancesofhighriskofbacterial infection whenitcomesincontactwitheyecells.Duetoinfection,manyimplantsfail, and thepatientrequiresimmediatesurgeryandthussuffersfrompost-operative problems. Toovercomethisproblem,ananti-bacterialdrugloadedvitreoussubstitute could beapromisingone. Toaddresstheaboveproblem,Iaimtodevelopasuitabletransparent polymeric hydrogelwhichcanactasanidealAVS,thatwillperformthefunctionof natural vitreous,tamponadetheretina,andpreventbacterialinfectionattheimplanted site. Firstly,Itriedtoexplorethepotentialofaloeverahydrogelextract(AVsolution) as avitreoussubstitute.Aloeveraisselectedbecauseitisanaturalherbalextractthat possesses transparency,highwatercontent(98%-99%),gel-formingproperty, anti-inflammatory,UVprotective,andantioxidant,properties.Itsrecentsuccessin treating cornealeyeinflammationledustouseitfortheapplicationofvitreous substitutes. Resultssuggestedthatthealoeveraextracthasslightlylowertransparency (>80%) ascomparedtothehumanvitreous(>90%).TheAVsolutionwasfound biocompatible. However,therheologicalpropertyoftheAVsolutiondoesnotmatch with thehumanvitreous.Thus,thisAVsolutioninitspresentformwasnotsuitableas a vitreoussubstitute. Secondly,thedifferenthydrogelformulationsofdeacetylatedhyaluronic acid-sodium salt(HA)crosslinkedwithdifferentconcentrationsofPESCEhadbeen developedasAVS.ResultsdepictedthatallthehydrogelformulationsofHA-PESCE havehighertransparency(>96%),highwatercontent(>96%),pH,R.I.valuesare closer tothehumanvitreoushumorandporousnature.Moreover,thehydrogel possesses suitableviscoelasticproperty(modulus>100Pa),andbiocompatibilitywith the NIH3T3mousefibroblastcellline.Thus,HA-PESCEmayserveasapotential AVS. In thethirdstudy,HA-PESCEhydrogelswereincorporatedwithcollagento bio-mimic thenaturalvitreous,improvingstabilityandbiocompatibility.Developed HA-Coll-PESCE hydrogelspossessin-situgelationcapability,transparency(>98%), improvedrheologicalproperty,highwatercontent(>96%),andbiocompatibilitywith the NIH3T3cellline.ThehydrogelformulationofHA-Coll-PESCE1(PESCE-10 mg) hasamaximumtransparencyandsuitablemodulus.Therefore, HA/collagen/PESCE 1hydrogelwillbeahighlysuitablevitreoussubstitute. Lastly,topreventbacterialinfectionwithintheimplantandattheimplanted site, theHA-PESCEhydrogelsweremodifiedbyincorporatingthedrugmeropenem within thehydrogelformulations.IncorporationofthedrugintoHA-Mer-PESCE hydrogelcausesaslightlyyellowishcolorofthehydrogelwithtransparency>90%, which isacceptableforvitreoussubstituteapplications.Thehydrogelformulation HA-Mer-PESCE3(PEG:30mg)andHA-Mer-PESCE4(PEG:40mg)bothhave almost similartransparency,highwatercontent,desirableviscoelasticproperty (modulus >100Pa)over1month,andbiocompatibilitywithNIH3T3mousefibroblast cell line.TheHA-Mer-PESCE3andHA-Mer-PESCE4,hydrogelshowedsimilar antibacterial effectsagainstgram-negativeandgram-positivebacteriaandallowedthe sustained releaseofthedrug.Thus,boththeformulationmayfindapplicationasAVS. Thus, fromtheabovestudy,itcanbestatedthatthealoeveraextractinits present formwasnotsuitableasavitreoussubstitute.However,HA-PESCE, HA-Coll-PESCE, andHA-Mer-PESCEhydrogels,successfullydeveloped,inthis study,mayserveaspotentialAVS.Inafurtherstudy,in-vivotestingneedstobe performed toevaluatethepotentialofthedevelopedhydrogelsfortheirclinical applications.