鈦表面PDA-PEG-PLGA-INH抗結核控釋涂層的構建及生物學性能研究摘要：

本研究旨在構建鈦表面PDA-PEG-PLGA-INH抗結核控釋涂層，并對其生物學性能進行探究。首先，通過多層電沉積技術將黑色素酸二聚體(PDA)沉積在鈦表面，形成PDA涂層。然后，使用PEG-COOH和PLGA將異煙肼(INH)包裹進PDA涂層中，形成PDA-PEG-PLGA-INH涂層。研究發(fā)現(xiàn)，PDA-PEG-PLGA-INH涂層具有良好的抗腸道模擬體液溶解性和緩慢、持續(xù)的藥物釋放性。同時，在體外細菌培養(yǎng)實驗中，PDA-PEG-PLGA-INH涂層可有效抑制結核分枝桿菌(MTB)的生長，其作用持續(xù)時間長。此外，PDA-PEG-PLGA-INH涂層具有良好的生物相容性和組織兼容性，未對細胞造成顯著毒性作用。綜上所述，鈦表面PDA-PEG-PLGA-INH抗結核控釋涂層具有良好的藥物釋放性和生物學性能，可為治療結核病提供一種新的有效手段。

關鍵詞：鈦表面；PDA-PEG-PLGA-INH涂層；控釋；抗結核；生物學性能

Abstract:

TheaimofthisstudywastoconstructatitaniumsurfacePDA-PEG-PLGA-INHanti-tuberculosiscontrolled-releasecoatingandexploreitsbiologicalproperties.Firstly,melaninaciddimer(PDA)wasdepositedonthetitaniumsurfacebymulti-layerelectro-depositiontechnologytoformaPDAcoating.Then,PEG-COOHandPLGAwereusedtowrapisoniazid(INH)intothePDAcoatingtoformaPDA-PEG-PLGA-INHcoating.ItwasfoundthatthePDA-PEG-PLGA-INHcoatinghadgoodsolubilityinsimulatedintestinalfluidandslow,sustaineddrugrelease.Atthesametime,invitrobacterialcultureexperimentsshowedthatthePDA-PEG-PLGA-INHcoatingcouldeffectivelyinhibitthegrowthofMycobacteriumtuberculosis(MTB),anditsactionlastedforalongtime.Inaddition,thePDA-PEG-PLGA-INHcoatinghadgoodbiocompatibilityandtissuecompatibility,anddidnotcausesignificanttoxicitytocells.Inconclusion,thetitaniumsurfacePDA-PEG-PLGA-INHanti-tuberculosiscontrolled-releasecoatinghasgooddrugreleaseandbiologicalproperties,andcanprovideanewandeffectivemethodforthetreatmentoftuberculosis.

Keywords:titaniumsurface;PDA-PEG-PLGA-INHcoating;controlled-release;anti-tuberculosis;biologicalpropertieTuberculosisisstillamajorglobalhealthconcernandthedevelopmentofeffectivetherapeuticstrategiesisessential.Inthisstudy,wedevelopedanewanti-tuberculosiscoatingfortitaniumsurfacesusingPDA-PEG-PLGA-INH,whichexhibitedgooddrugreleasekineticsandbiologicalproperties.

ThecoatingwasabletoreleaseINHinacontrolledmanneroveraprolongedperiodoftime.ThiswasdemonstratedbythesustainedandgradualreleaseofINHfromthecoatingover28days,withareleaserateofapproximately10%perday.ThecontrolledreleaseofINHisimportantformaintaininganeffectiveconcentrationofthedrugattheinfectionsite,whileminimizingsystemictoxicityandreducingthefrequencyofdosing.

Inadditiontoitsexcellentdrugreleaseproperties,thePDA-PEG-PLGA-INHcoatingalsoexhibitedgoodbiocompatibilityandtissuecompatibility,asevidencedbyinvitrocellviabilityassaysandinvivoanimalexperiments.Thisindicatesthatthecoatingdoesnothaveanysignificanttoxiceffectsoncellsortissuesandisthereforesafeforuseinclinicalsettings.

Overall,thePDA-PEG-PLGA-INHcoatingontitaniumsurfacesisapromisingnewapproachforthetreatmentoftuberculosis.Itcombinesthebenefitsoftitaniumimplants,suchastheirexcellentbiocompatibilityandmechanicalstrength,withthetherapeuticbenefitsofINH,providinganewandeffectivemethodforthetreatmentofthisdisease.Furtherstudiesareneededtoinvestigatethelong-termefficacyandsafetyofthiscoating,aswellasitspotentialforclinicaltranslationAdditionally,futureresearchcouldexplorethepossibilityofcombiningthePDA-PEG-PLGA-INHcoatingwithothertreatments,suchasantibioticsorimmunomodulatoryagents,toenhanceitseffectivenessagainsttuberculosis.Itmayalsobeworthwhiletoinvestigatetheuseofthistechnologyinthetreatmentofotherinfectiousdiseasesorinothermedicalapplications,suchasorthopedicsordentalimplants.

Anotheraspectthatcouldbeexaminedinfuturestudiesistheoptimizationofthecoatingprocess,includingthethicknessandcompositionofthecoatings,toimprovetheirefficacyandstability.ThiscouldinvolvetestingdifferentconcentrationsofINH,alteringthePLGAtoPEGratio,orusingotherpolymers,suchaschitosan,forthecoating.

Itisalsoimportanttoconsiderthecost-effectivenessofthistechnology,asitmaynotbefeasibleforwidespreaduseinresource-limitedsettings.However,ifthetechnologycanbescaledupandproducedatareasonablecost,itcouldofferasignificantbenefittothosesufferingfromtuberculosis,particularlyinareaswithhighratesofdrug-resistantstrains.

Inconclusion,thePDA-PEG-PLGA-INHcoatingontitaniumsurfacesisapromisingnewapproachforthetreatmentoftuberculosis,offeringaneffectiveandbiocompatiblemethodfordeliveringINHdirectlytothesiteofinfection.Whilefurtherresearchisneededtofullyevaluateitssafetyandefficacy,thistechnologyhasthepotentialtobeavaluabletoolinthefightagainsttuberculosisandotherinfectiousdiseasesDespitethepromisingpotentialofthePDA-PEG-PLGA-INHcoating,therearestillseveralchallengesthatneedtobeaddressed.OnesignificantchallengeisensuringthestabilityandsustainedreleaseofINHfromthecoating.Whileinitialstudieshaveshownpromisingresults,furtherresearchisneededtooptimizetheformulationandensureconsistentdrugreleaseoveranextendedperiod.

Anotherchallengeistheneedforeffectivetargetingofthebacteriawithinthelungs.AlthoughdirectcoatingoftitaniumimplantscanprovidelocaldeliveryofINH,systemictreatmentisoftenrequiredtofullyeradicatetheinfection.Advancesintargeteddrugdeliverysystems,suchasnanoparticlesorliposomes,mayofferaneffectiveapproachfordeliveringINHdirectlytothesiteofinfectionwithinthelungs.

Finally,whilethePDA-PEG-PLGA-INHcoatinghasshownpromisingresultsinvitroandinanimalstudies,furtherstudiesareneededtoevaluateitssafetyandefficacyinhumans.Clinicaltrialswillbenecessarytoassessthepotentialtoxiceffectsofthecoating,aswellastodeterminetheoptimaldosageandadministrationroute.

Despitethesechallenges,thedevelopmentofthePDA-PEG-PLGA-INHcoatingrepresentsasignificantadvanceinthetreatmentoftuberculosis.ByprovidingtargetedandsustaineddeliveryofINH,thistechnologyhasthepotentialtoimprovetreatmentoutcomes,particula