口服奈米載體之基因傳遞研究__臺灣博碩士論文知識加值系統

胜肽,奈米管、基因傳遞、口服,peptide nanotube,gene delivery,oral,口服奈米載體之基因傳遞研究. 資料載入處理中... 跳到主要內容 臺灣博碩士論文加值系統 ::: 網站導覽| 首頁| 關於本站| 聯絡我們| 國圖首頁| 常見問題| 操作說明 English |FB專頁 |Mobile 免費會員 登入| 註冊 功能切換導覽列 (165.22.106.144)您好！臺灣時間：2022/09/0501:02 字體大小：       ::: 詳目顯示 recordfocus 第1筆/ 共1筆  /1頁 論文基本資料 目次 參考文獻 電子全文 紙本論文 QRCode 本論文永久網址: 複製永久網址Twitter研究生:謝緯賢研究生(外文):Wei-HsienHsieh論文名稱:口服奈米載體之基因傳遞研究論文名稱(外文):OralGeneDeliverywithNano-Carrier指導教授:廖嘉鴻指導教授(外文):Jia-HorngLiaw學位類別:博士校院名稱:臺北醫學大學系所名稱:藥學系(博士班)學門:醫藥衛生學門學類:藥學學類論文種類:學術論文論文出版年:2012畢業學年度:100語文別:中文論文頁數:101中文關鍵詞:胜肽、奈米管、基因傳遞、口服外文關鍵詞:peptidenanotube、genedelivery、oral相關次數: 被引用:0點閱:167評分:下載:0書目收藏:0 目錄i中文摘要viABSTRACTviii壹、緒論1一、基因傳遞1二、載體（Vector）31.病毒型載體42.非病毒型載體4貳、研究目的10参、材料與方法11一、實驗試藥11二、儀器與耗材12三、溶液的配製131.Ethidiumbromide(10mg/ml)132.NaOH(10N)133.Tris-Cl(1M;pH7.4)134.EDTA(0.5M;pH8.0)135.10XTrisEDTA(TE)136.1XTrisEDTA(TE)137.50XTAEbuffer148.1XTAEworkingsolution149.20%SDS1410.PBS1411.SolutionI1412.SolutionII1413.SolutionIII1414.Pnenol1415.CIAA1516.20mOsm1517.LBMedium1518.X-galsolution1519.20XSSC1520.Denaturebuffer1521.Neutralizedbuffer1522.Washingbuffer11623.Washingbuffer21624.SolutionA1625.SolutionB1626.SolutionC1627.顯影劑1628.定影劑16四、研究方法161.製備胜肽奈米管172.質體DNA的製備173.TM-Rhodamine標記質體DNA184.鑑定TM-Rhodamine標記pCMV-LacZ185.製備質體DNA混合胜肽奈米管186.掃描式電子顯微鏡（Scanningelectronmicroscope;SEM）187.穿透式電子顯微鏡（Transmissionelectronmicroscope;TEM）198.原子力顯微鏡（Atomicforcemicroscope;AFM）199.臨界聚合濃度（Criticalassociationconcentration;CAC）1910.粒徑及介面電位（Zetapotential）測量2011.TM-rhodamine標記之pCMV-LacZ混合胜肽奈米管後之螢光評估2012.螢光光譜偵測2113.pCMV-LacZ於胜肽奈米管上之承載效率（Loadingefficiency）評估2114.pCMV-LacZ於混合胜肽奈米管後之釋放速率2215.pCMV-LacZ混合胜肽奈米管之安定性試驗2216.胜肽奈米管之安定性試驗2317.實驗動物2318.離體十二指腸穿透試驗2319.活體動物口服投予2520.組織萃取及基因表現測定2521.南方墨點法析2722.組織中之mRNA萃取2923.組織切片3024.活體外（Exvivo）生物冷光偵測31肆、結果33一、物理化學特性331.胜肽奈米管332.pCMV-LacZ標記TM-rhodamine373.pCMV-LacZ混合胜肽奈米管39二、DNA於胜肽奈米管之承載量44三、DNA於胜肽奈米管之釋放速率45四、胜肽奈米管於人工胃液之安定性評估45五、DNA與胜肽奈米管混合後之安定性評估46六、DNA於十二指腸的穿透評估49七、裸鼠口服投予pCMV-LacZ混合胜肽奈米管511.β–Gal酵素活性評估512.胜肽奈米管於胃、十二指腸、肝臟及腎臟之分佈533.pCMV-LacZ於胃、十二指腸、肝臟及腎臟之分佈554.南方墨點法（Southernblot）分析DNA完整性595.mRNA分析606.組織切片62八、裸鼠口服投予pCMV-hRluc混合胜肽奈米管651.mRNA分析652.活體外（Exvivo）生物冷光偵測673.水母冷光酵素活性評估674.組織切片70伍、討論72一、胜肽奈米管72二、質體DNA混合胜肽奈米管721、質體DNA結合胜肽奈米管722、質體DNA混合胜肽奈米管後之安定性723、質體DNA混合胜肽奈米管後於十二指腸之穿透734、裸鼠口服投予質體DNA混合胜肽奈米管74陸、結論76柒、參考文獻77圖表目錄Figure1.Fluorescencespectrumofpyrene..20Figure2Morphologyofpeptidenanotubes(PNTs)..34Figure3Self-associationandsizedistributionofpeptidenanotubes(PNTs)..35Figure4IdentificationofTM-rhodaminelabeledpCMV-LacZbyhighperformanceliquidchromatography(HPLC)withUVdetectorabsorbedat260nm..37Figure5IdentificationofTM-rhodaminelabeledpCMV-LacZbyhighperformanceliquidchromatography(HPLC)withfluroscencedetectorexcitatedat546nmandemittedat576nm.38Figure6Zetapotentialanalysisofpeptidenanotubes(PNTs)(A),pCMV-LacZ(B),andpCMV-LacZformulatedwithPNTs(C).39Figure7MorphologiesofpCMV-LacZaloneandpCMV-LacZformulatedwithpeptidenanotubes(P/PNTs)..40Figure8FluorescencemicroscopeimagingofTM-rhodaminelabeledpCMV-LacZformulatedwithpeptidenanotubes(P/PNTs)..41Figure9Fluorescencequenchingassayofpeptidenanotubes(PNTs)withpCMV-LacZ(P)..43Figure10TheamountofpCMV-LacZ(P)absorbedwithpeptidenanotubes(PNTs)andthereleaseprofileofnakedpCMV-LacZandpCMV-LacZformulatedwithPNTs(P/PNTs)..45Figure11Stabilityofpeptidenanotubes(PNTs)withsimulatedgastricacidtreatment..46Figure12StabilityofpCMV-LacZ(P)(7.2kb)withpeptidenanotubes(PNTs)analyzedbyDNaseI,acid,andbiledigestion..48Figure13Thehistologicalanalysisofpeptidenanotubes(PNTs)distributionintissuesofnudemiceafter1horallydeliverywiththioflavinT(ThT)pre-stainedPNTs..54Figure14Thehistologicalanalysisofdegradedpeptidenanotubes(PNTs)distributionintissuesofnudemiceafter1horallydeliverywiththioflavinT(ThT)pre-stainedPNTs..55Figure15ThehistologicaldistributionofTM-rhodamine-labeledpCMV-LacZintissuesofnudemiceafter1horaldeliverywithTM-rhodamine-labeledpCMV-LacZformulatedwithpeptidenanotubes(P/PNTs)..57Figure16SouthernblotanalysisoftissueDNAsfrommiceorallyadministratedwithnakedpCMV-LacZ(P)(7.2kb)orpCMV-LacZformulatedwithpeptidenanotubes(P/PNTs)asafunctionoftime..59Figure17StandrdcurveofpCMV-LacZmeasuredbyrealtimeqPCR..61Figure18Thewholemount(WM)andhistologicalanalysisofX-galstainingoftissuesofnudemiceafterorallydeliverywithpCMV-LacZformulatedwithpeptidenanotubes(P/PNTs)..63Figure19StandrdcurveofpCMV-hRlucmeasuredbyrealtimeqPCR..66Figure20ExvivobioluminescenceimagingofmicetissuesafterorallyadministratedwithpCMV-hRlucformulatedwithpeptidenanotubes(P/PNTs)..67Figure21ImmunohistologicalanalysisoftissuesofnudemiceafterorallyadministratedwithpCMV-hRlucformulatedwithpeptidenanotubes(P/PNTs)..71Table1SizeandZetapotentialofpCMV-LacZ(P)formulatedwithpeptidenanotubes(PNTs).36Table2ApparentpermeabilitycoefficientofpCMV-LacZ(P)formulatedwithpeptidenanotubes(PNTs).50Table3Theβ-GalactivitiesinnudemicetissuesafteroraldeliverywithpCMV-LacZ(P)/peptidenanotubes(PNTs)52Table4mRNAlevelinnudemicetissuesafteroraldeliverywithpCMV-LacZformulatedwithpeptidenanotubes61Table5mRNAlevelinnudemicetissuesafteroraldeliverywithpCMV-hRlucformulatedwithpeptidenanotubes66Table6TheRenillaluciferaseactivityintissuesofnudemiceafterorallydeliverywithpCMV-hRluc(P)/peptidenanotubes(PNTs)69 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