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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳進庭 | zh_TW |
| dc.contributor.advisor | Chin-Tin Chen | en |
| dc.contributor.author | 盧傳恩 | zh_TW |
| dc.contributor.author | Chuan-En Lu | en |
| dc.date.accessioned | 2021-07-11T15:19:32Z | - |
| dc.date.available | 2024-06-30 | - |
| dc.date.copyright | 2019-07-01 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Phillips, R.M., Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs. Cancer chemotherapy and pharmacology, 2016. 77(3): p. 441-457.
Rainer, H.M., S. Ranjita, and M.K. Cornelia, 20 Years of Lipid Nanoparticles (SLN & NLC):Present State of Development & Industrial Applications. Current Drug Discovery Technologies, 2011. 8(3): p. 207-227. Iqbal, M.A., et al., Nanostructured lipid carriers system: Recent advances in drug delivery. Journal of Drug Targeting, 2012. 20(10): p. 813-830. Fernandes, R.S., et al., Doxorubicin-loaded nanocarriers: A comparative studyliposome and nanostructured lipid carrier as alternatives for cancer therapy. Biomedicine & Pharmacotherapy, 2016. 84: p. 252-257. Ding, X., et al., Tumor targeted nanostructured lipid carrier co-delivering paclitaxel and indocyanine green for laser triggered synergetic therapy of cancer. RSC Advances, 2017. 7(56): p. 35086-35095. Bader, M., A systematic approach to standard addition methods in instrumental analysis. ournal of Chemical Education, 1980. 57(10): p. 703. Moulai-Mostefa, N. and A. Boumenir, Formulation of a Stable Multiple Emulsion via a One Step Process Using Surface Properties of the Mixed Emulsifiers. Journal of D Dispersion Science and Technology, 2010. 32(1): p. 102-108. Yu, A., et al., Formulation Optimization and Bioavailability After Oral and NasalAdministration in Rabbits of Puerarin-Loaded Microemulsion. Journal ofPharmaceutical. Sciences, 2011. 100(3): p. 933-941. Fang, C., S. Al-Suwayeh, and J.-Y. Fang, Nanostructured Lipid Carriers (NLCs) for Drug. Delivery and Targeting. Vol. 7. 2012. Müller, R.H., M. Radtke, and S.A. Wissing, Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Advanced Drug Delivery. Reviews, 2002. 54: p. S131-S155. Zhao, S., et al., Doxorubicin hydrochloride-oleic acid conjugate loaded nanostructured lipid carriers for tumor specific drug release. Colloids and Surfaces B: Biointerfaces, 2016. 145: 95-103. Jaiswal, P., B. Gidwani, and A. Vyas, Nanostructured lipid carriers and their current application in targeted drug delivery. Artificial Cells, Nanomedicine, and B iotechnology, 2016. 44(1): p. 27-40. Ghasemiyeh, P. and S. Mohammadi Samani, Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages. Vol. 13.,2018. Goodrum, J.W. and D.P. Geller, Influence of fatty acid methyl esters from hydroxylated vegetable oils on diesel fuel lubricity. Bioresource Technology, 2005.96(7): p. 851-855. Kasongo, K.W., R.H. Müller, and R.B. Walker, The use of hot and cold high pressure homogenization to enhance the loading capacity and encapsulation efficiency of nanostructured lipid carriers for the hydrophilic antiretroviral drug, didanosine for potential administration to paediatric patients. Pharmaceutical Development and Technology, 2012. 17(3): p. 353-362. Tamjidi, F., et al., Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules. Innovative Food Science & Emerging Technologies, 2013. 19: p. 29-43. Shen, Y.A., et al., Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control. International journal of nanomedicine, 2015. 10: p. 2485-2502. Kagan, L., et al., Dual Physiologically Based Pharmacokinetic Model of Liposomal and Nonliposomal Amphotericin B Disposition. Pharmaceutical Research, 2014. 31(1): p. 35-45. Cowen, R.L., et al., Hypoxia Targeted Gene Therapy to Increase the Efficacy of Tirapazamine, as an Adjuvant to Radiotherapy. Cancer Research, 2004. 64(4): p. 1396. Lunt, S.J., et al., Tirapazamine Administered as a Neoadjuvant to Radiotherapy Reduces. Metastatic Dissemination. Clinical Cancer Research, 2005. 11(11): p. 4212. Emmenegger, U., et al., Low-Dose Metronomic Daily Cyclophosphamide and Weekly Tirapazamine: A Well-Tolerated Combination Regimen with Enhanced Efficacy That Exploits. Tumor Hypoxia. Cancer Research, 2006. 66(3): p. 1664. Gatzemeier, U., et al., Tirapazamine-cisplatin: the synergy. British journal of cancer, 1998. 77. Suppl 4(Suppl 4): p. 15-17. Rischin, D., et al., Tirapazamine, Cisplatin, and Radiation Versus Fluorouracil, Cisplatin, and Radiation in Patients With Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02). Journal of Clinical. Oncology, 2005. 23(1): p. 79-87. Walton, M.I. and P. Workman, Pharmacokinetics and bioreductive metabolism of the novel benzotriazine di-N-oxide hypoxic cell cytotoxin tirapazamine (WIN 59075; SR 4233; NSC 130181) in mice. Journal of Pharmacology and Experimental Therapeutics, 1993. 265(2): p. 938. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78790 | - |
| dc.description.abstract | Hypoxia-activated Prodrug X (HAPX) 是一種被發展做為治療具有抗藥性腫瘤的藥物。然而，它在臨床使用上有幾個障礙，包含體內半衰期短、低溶解度、低腫瘤累積量以及低患者依從性等特性。這項研究的目的是建立脂質載體 (lipid-based carriers) 來包覆HAPX以解決上述問題。脂質載體的製備方式，採用了低溫乳化法 (cold emulsification method) 搭配inverse micelleformation以提升HAPX的包覆率，並以HPLC來分析HAPX在經過劑型製備以及長期儲存後是否會發生降解的情形以及脂質載體的穩定性。雖然細胞實驗顯示以脂質載體包覆HAPX後，對C26細胞的毒性雖然與未包覆的HAPX相當，但體內組織分佈研究卻發現，HAPX經過脂質載體包覆後，其在腫瘤部位比起未包覆的HAPX有更顯著的累積量，而且顯著提升了腫瘤的抑制能力和降低了HAPX的副作用。 | zh_TW |
| dc.description.abstract | Hypoxia-activated prodrugX (HAPX) has been developed for the treatment of chemotherapy-resistant tumor. Several obstacles of HAPX have been found in the clinical use, such as short half-life in bodies, unfavorable physical characteristics of low solubility, low partition coefficient and low patient compliance. The purpose of this study was to overcome these obstacles by developing a lipid-based carrier to deliver HAPX. The adopted strategy utilizes inverse micelle formation and the cold emulsification method to enhance the entrapment efficiency of HAPX. Drug degradation and long-term storage stability of HAPX in this lipid-based carriers were performed through HPLC analysis. To evaluate the therapeutic efficacy, in vitro and in vivo studies were conducted. Although the in vitro studies showed that HAPX in lipid-based carriers possessed insignificant cytotoxic effects on C26 cells, the in vivo tissue distribution studies demonstrated that the accumulation of HAPX in lipid-based carriers is significantly higher than that of free-form HAPX in tumor site. The in vivo therapeutic efficacy was conducted in C26 tumor-bearing mice. Mice treated with lipid-based carriers containing HAP showed greater tumor suppression ability than the mice group which received free-from HAPX. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:19:32Z (GMT). No. of bitstreams: 1 ntu-108-R06b22007-1.pdf: 2335065 bytes, checksum: cd852b0d211b90c927beeef9f1dd67c2 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | LIST OF CONTENTS
Abbreviation table 1 中文摘要 2 Abstract 3 Chapter 1 Introduction 4 1.1 Tumor hypoxia and drug-resistance 4 1.2 Hypoxia-activated prodrug 5 1.3 Nanostructured lipid carriers (NLCs) 7 1.4 Research motivation 9 Chapter 2 Materials and Methods 10 2.1 Materials 10 2.2 Apparatus 11 2.3 HPLC condition 11 2.4 Standard addition method 12 2.5 Solubility study of HAPX in different solvents 12 2.6 Preparation of NLCs 13 2.7 Entrapment efficiency and loading capacity 13 2.8 Particle Size and morphology 14 2.9 Stability tests of long-term storage 15 2.10 In vitro study 15 2.11 Lyophilization 16 2.12 X-ray diffraction 16 2.13 Tissue distribution and pharmacokinetic studies 16 2.14 In vivo therapeutic efficacy 18 2.15 Statistical Analysis 19 Chapter 3 Results 20 3.1 Selection of lipid 20 3.2 NLC formula determination 20 3.3 The establishment and optimization of NLC preparing process 21 3.4 Determination of particle size and morphology 22 3.5 Long-term stability of NLC-HAPX at room temperature 23 3.8 Long-term stability of lyophilized NLC-HAPX at Room Temperature 25 3.9 X-ray diffraction (XRD) analysis 26 3.10 Tissue distribution and pharmacokinetic studies 27 3.11 In vivo therapeutic efficacy 28 Chapter 4 Discussion 30 4.1 NLC formula determination and preparing optimization 30 4.2 Particle Size, morphology and crystallinity of NLC-HAPX 31 4.3 In vitro study 33 4.4 Tissue distribution and pharmacokinetic studies of NLC-HAPX 34 4.5 In vivo therapeutic efficacy 37 Chapter 5 Conclusion 39 Chapter 6 Reference 60 LIST OF FIGURES Figure 1. HPLC chromatograms of mixture of HAPX and its degraded forms 40 Figure 2. Solubility test of HAPX at 37 ° C. 41 Figure 3. Morphology of NLC-HAPX 42 Figure 4. Stability of HAPX after completion of NLC preparation 43 Figure 5. Stability studies of NLC-HAPX after completion of NLC preparation 44 Figure 6. Cytotoxicity study of HAPX on C26 cell line 45 Figure 7. Stability of HAPX after completion of NLC-HAPX lyophilization 46 Figure 8. Stability studies of NLC-HAPX after lyophilization 47 Figure 9. X-ray diffraction analysis 48 Figure 10. Tissue distribution studies of drug treatment with i.p. administration. 49 Figure 11. Area under the curves (AUCs) of NLC-HAPX and free-form HAPX in the tumor, liver, spleen and kidney. 50 Figure 12. Therapeutic efficacy of combination therapy of HAPX and stilbene 5c in C26 syngeneic BALB/c tumor model. 51 Figure 13. Anticancer efficacy of PBS and combination therapy of HAPX and stilbene 5c. 52 Picture 1. Nanostructured lipid carrier (NLC) …………………………………………53 Picture 2. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) with different crystallinity …………………..…………………………………………54 Scheme 1.NLC-HAPX preparation by hot emulsification method…………………….55 Scheme 2. NLC-HAPX preparation by cold emulsification method.....……………….55 LIST OF TABLES Table 1. Compositions of NLC-HAPX with different formulae 56 Table 2. Characteristics of NLCs manufactured by cold emulsification method and hot emulsification method 57 Table 3. Physicochemical properties of the NLC-HAPX before and after lyophilization with different cryoprotectants 58 Table 4. Pharmacokinetic parameters of HAPX after i.p. administration. 59 | - |
| dc.language.iso | en | - |
| dc.title | 開發用於遞送缺氧選擇性藥物之奈米脂質載體 | zh_TW |
| dc.title | Development of lipid-based carriers for Hypoxia-activated prodrug X | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 吳?承;廖泰慶;謝堅銘 | zh_TW |
| dc.contributor.oralexamcommittee | HSUAN-CHEN WU;TAI-CING LIAO;Chien-Ming Hsieh | en |
| dc.subject.keyword | 缺氧選擇性藥物,脂質載體, | zh_TW |
| dc.subject.keyword | Hypoxia-activated prodrug,Lipid-based carriers, | en |
| dc.relation.page | 64 | - |
| dc.identifier.doi | 10.6342/NTU201901015 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-06-25 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | 2024-06-30 | - |
| 顯示於系所單位： | 生化科技學系 | |
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