高强度温敏性水凝胶的合成与性能研究学位论文完成日期:指导教师签字:答辩委员会成员签字:
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万方数据高强度温敏性水凝胶的合成与性能研究摘要温敏性水凝胶聚N.异丙基丙烯酰胺(PNIPAAm)是研究和应用最为广泛的一种刺激响应性水凝胶,当外界温度在其低临界溶解温度(LCST)附近发生微小变化时,温敏性水凝胶能够表现出明显的相转变性能,近年来很多研究者报导了其在生物医学方面的潜在应用,如药物控释、生物分离等。但是PNIPAAm水凝胶的力学性能较差,使其在组织工程领域的应用受到限制,制备互穿网络(IPN)结构是提高水凝胶力学强度的有效方法。本文为了提高温敏性水凝胶PNIPAAm的力学性能和生物相容性,首先在PNIPAAm聚合物网络中引入天然高分子海藻酸钠(SA),制备半互穿网络(semi.IPN)水凝胶,然后以Ca2+交联SA与PNIPAAm互相穿插形成全互穿网络(full.IPN)水凝胶,系统考察海藻酸钠的加入对PNIPAAm水凝胶压缩强度、拉伸强度、扯断伸长率等力学性能的改善作用,对两种水凝胶的温敏性能、溶胀性能做了研究,并初步考察了水凝胶的药物控释性能。1、将SA分子链缠结到PNIPAAm网络中形成半互穿网络水凝胶,SA对水凝胶的LCST没有显著影响;以Ca2+交联SA与PNIPAAm互相穿插形成全互穿网络水凝胶,使水凝胶的LCST有微弱升高,由33℃升高至1]34℃左右。2、所有水凝胶在25℃的蒸馏水中具有较快的溶胀速率,并且SA用量越高,溶胀性能越好;全互穿网络水凝胶的溶胀率有略微降低。水凝胶在PBS中溶胀性能优于在模拟胃液中的溶胀性能。3、盐溶液中离子强度对水凝胶的溶胀性能具有较大影响,在NaCI浓度低于0.07mg/mL的盐溶液中两种水凝胶均具有较好的溶胀性能,当NaCI浓度高于0.07
mg/mL时,水凝胶的溶胀度明显降低。4、水凝胶在45℃的蒸馏水中具有较快的退溶胀速率,并且SA用量和Ca2+用量越多,退溶胀速率越低。5、半互穿网络水凝胶的压缩强度高于PNIPAAm水凝胶,并且在一定范围内,随着SA用量的增加其压缩强度逐渐升高。相对于半互穿网络水凝胶,全互穿网络水凝胶的压缩强度和拉伸强度明显提高,随着Ca2+用量的增加,其力学强度明显提高。6、热失重实验表明两种水凝胶均具有良好的热稳定性。互穿网络水凝胶的玻璃化转变温度明显高于PNIPAAm水凝胶,证明成功形成互穿网络结构。
万方数据7、扫描电镜观察发现两种水凝胶均具有均一的孔洞结构,有助于水分子进出水凝胶。8、对5-Fu的释放研究表明:半互穿网络载药水凝胶中SA含量越多,药物释放速率越快;全互穿网络载药水凝胶对药物释放缓慢,可达到缓释效果。温度对释放速率有一定影响,25℃时释放缓慢,37℃时出现“暴释”现象;介质pH对释放速率有一定影响,在PBS中的释放速率大于在模拟胃液中的释放速率。
关键词:温敏性水凝胶Ⅳ.异丙基丙烯酰胺互穿网络海藻酸钠机械强度
万方数据SYNTHESISANDCHARACTERIZATIoNoF
THERMOSENSITIVEHYDRoGELWITH
IMPROVED
MECHANICALPROPERTIES
ABSTRACTP(N-isopropylacrylamide)(PNlPAAm)isoneofthemost
widelystudied
thermo-sensitivehydrogels,exhibitingareversiblephasetransitioninaqueous
solutionsatalowercriticalsolutiontemperature(LCST).Many
investigatorshave
reportedonthepotentialofPNIPAAmhydrogelsforuseinseveralbiomedicalapplications,includingdrugdelivery,bioseparation
and
SO
on.However,an
important
limitationofPNIPAArnhydrogelsforapplicationistheirpoormechanicalproperties.
Preparationofinterpenetratingpolymernetwork(IPN)structureisaneffectivemethodtoimprove
themechanicalstrengthofthe
hydrogel.
Inthispaper,inordertoimprovethemechanicalpropertiesandbiocompatibility
ofthethermosensitivePNIPAAmhydrogel,firstlynaturalpolysaccharidessodium
alginate(SA)WasintroducedintothePNIPAAmbackboneto
formSA/PNIPAAm
semi—IPNhydrogel.thenCa-alginatepolymerWaspreparedbycrosslinking
ofSAwith
Ca2+ions,andfull-IPNhydrogelwassynthesizedbywhich
Ca-alginate
Was
entangled
withPNIPAAm.Theimprovementofcompressivestrength,tensilestrengthand
ElongationatBreakofthesemi·IPNandfull-IPNhydrogelswerestudied.Andtemperaturesensitivity,swelling/deswellingbehaviorsandthepreliminarystudyof
drugreleaseofthesetwokindsofhydrogelswereinvestigatedrespectively.
1.ThelinercopolymerSAwasentangledwithPNIPAAmnetwork,which
hadno
obviouseffectontheLCSTofthesemi..IPNhydrogel;TheLCSTofthefull..IPN
hydrogelwithCa-alginateandPNIPAAmincreasedto34℃.
2.Allthehydrogelsexhibitedfastswellingindistilledwaterat
25℃.and
the
swellingratioofthehydrgelsWasincreasedwiththeincreaseofSAcontent.The
swellingratiooffull—IPNhydrogelwassmallerthansemi—IPNhydrogelslightly.The
万方数据swellingpropertiesofthesetwokindsofhydrogelsinPBSwerebetterthanthatinsimulatedgastricfluid.3.IonicstrengthofthesaltsolutionhadagreatinfluenceOil
the
swelling
propertiesofthesetwokindsofhydrogels.TheswellingratioofthehydrogelswasdecreasedsharplywithincreasingNaClconcentrationto0.07mg/mL
at
25℃.
4.ThehydrogelsdeswelledfastinDWwhenthetemperaturewasabovetheirLCSTs.ThedeswellingrateofthehydrogelswasdecreasedwiththeincreaseofSAandCa2十content.5.Thecompressivestrengthofsemi-IPNhydrogelwashigherthanpure
PNIPAAm,andthecompressivestrengthofthehydrgelsWasincreasedwiththe
increaseofSAcontent.Full—IPNhydrogelshadhighercompressivestrengthandtensilestrength,andthemechanicalstrengthofthehydrgelsWasincreasedwiththeincreaseofCa2+content.6.Thethermody‘namicstabilityofthehydrogelsWaScharacterizedby
thermogravimetry.Theresultshowedthatthehydrogelhadagoodthermalstability.
Theglasstransitiontemperature(哟offull—IPNandsemi-IPNhydrogelswerehigher
thanthatofPNIPA.Am
hydrogels.ItWasintimatedthesuccessfulintroductionofSA
andCa-alginate.
7.ThemorphologyofhydrogelsWasestimatedbyfieldSCanelectronmicroscopy
(SEM).Thehydrogelscontainedopenandwell-structureorientatedporous
network.
8.ApreliminarystudyofIPNhydrogelsasthedrugdeliverysystemforthemodeldrug,5-fluorouracil(5-Fu)Wasperformed.Itwasfoundthatthereleaserate
and
amountof5一FuincreasewithincreasingSAcontentinthesemi-IPNhydrogel.The
releaseof5-Fuinfull-IPNhydrogelwagslowerthanthatofsemi-IPNhydrogel.
TemperatureandpHofthemediumhadeffectonthereleasebehaviors.
KEYWORDS:thermosensitivehydrogelN-isopropylacrylamide