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研究生:彭楷宸
研究生(外文):Kai-Chen Peng
論文名稱:評估包覆疏水性抗癌藥物之聚縮酮微奈米顆粒對抑制二維及三維肺癌細胞之效果
論文名稱(外文):Evaluation the Inhibitory Effect of Hydrophobic Anti-Cancer Drugs Loaded Polyketal Nano- and Microparticles on 2D- and 3D- Lung Cancer Cell Models
指導教授:高震宇高震宇引用關係
指導教授(外文):Chen-Yu Kao
口試委員:鄭智嘉李曉屏
口試委員(外文):Chih-Chia ChengShiao-Pieng Lee
口試日期:2020-07-20
學位類別:碩士
校院名稱:國立臺灣科技大學
系所名稱:醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:103
中文關鍵詞:聚縮酮奈米顆粒微米顆粒非小細胞肺癌細胞薑黃素厚朴酚伊維菌素
外文關鍵詞:PolyketalPCADKmicroparticles ( MPs )nanoparticles ( NPs )A549CurcuminMagnololIvermectin
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  • 點閱點閱:105
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論文摘要 1
Abstract 2
致謝 3
目錄 4
圖目錄 7
表目錄 12
第一章 緒論 1
第二章 文獻回顧 3
2.1癌症 3
2.1.1 肺癌 4
2.1.2非小型肺癌細胞A549 5
2.1.3 3D型態細胞模型 6
2.2 藥物傳輸系統 8
2.2.1 肺部藥物傳輸 9
2.2.2 藥物顆粒大小對肺部之吸收影響 10
2.2.3聚縮酮 ( Polyketal ) 藥物載體 11
2.3 厚朴酚 ( Magnolol ) 12
2.4 薑黃素 ( Curcumin ) 14
2.5 伊維菌素( Ivermectin ) 16
第三章 實驗材料與方法 18
3.1 研究設計 18
3.1.1 實驗理論 18
3.1.2 實驗設計 19
3.2 實驗材料與試劑及設備 20
3.2.1 高分子聚合物及顆粒製備材料與試劑 20
3.2.2 細胞培養之材料及試劑 20
3.2.3 實驗分析儀器設備 21
3.3 PCADK共聚物合成 22
3.4 PCADK共聚物包覆Curcumin、Magnolol及Ivermectin顆粒製作 23
3.4.1 PCADK共聚物包覆Magnolol奈米顆粒製作 23
3.4.2 PCADK共聚物包覆Curcumin奈米及微米顆粒製作 23
3.4.3 PCADK共聚物包覆Ivermectin奈米及微米顆粒製作 24
3.5 微米、奈米顆粒載體分析 25
3.5.1 微米及奈米顆粒表面型態及尺寸觀察 25
3.5.2 顆粒藥物包覆率計算 25
3.5.3 顆粒藥物體外釋放率計算 27
3.6 細胞培養 30
3.6.1 細胞培養條件及培養基配製 30
3.6.2 細胞凍存及活化 30
3.6.3 細胞培養基更換 31
3.6.4 細胞繼代 31
3.6.5 細胞毒性分析MTT Assay 32
第四章 結果 34
4.1 Polyketal 共聚物合成評估 34
4.1.1 Polyketal 共聚物組成分析 34
4.1.2 Polyketal 共聚物分子量分析 35
4.1.3 Polyketal 共聚物產率評估 37
4.2 藥物顆粒性質評估 37
4.2.1 顆粒型態分析 37
4.2.2 顆粒粒徑分析 46
4.2.3顆粒藥物包覆率分析 51
4.2.4 polyketal共聚物顆粒體外藥物釋放評估 52
4.2.5 polyketal共聚物顆粒懸浮評估 60
4.3 細胞實驗 62
4.3.1 細胞型態 62
4.3.2 細胞毒性分析 65
4.3.3 DAPI螢光染色 77
第五章 討論 78
5.1 Polyketal共聚物合成評估 78
5.2 藥物載體性質評估 78
5.3 體外細胞實驗評估 81
第六章 結論 84
第七章 參考文獻 85
1. Bray, F., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 2018. 68(6): p. 394-424.
2. Zarogoulidis, K., Treatment of non-small cell lung cancer (NSCLC). Journal of Thoracic Disease, 2013. 5 Suppl 4(Suppl 4): p. S389-S396.
3. Jemal, A., Cancer statistics, 2008. CA: A Cancer Journal for Clinicians, 2008. 58(2): p. 71-96.
4. Foster, K.A., Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. Experimental Cell Research, 1998. 243(2): p. 359-366.
5. Chen, Y.-H., Magnolol: A multifunctional compound isolated from the Chinese medicinal plant Magnolia officinalis. European Journal of Integrative Medicine, 2011. 3(4): p. e317-e324.
6. Lo, Y.-C., Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochemical Pharmacology, 1994. 47(3): p. 549-553.
7. Seo, J.-U., Anticancer potential of magnolol for lung cancer treatment. Archives of Pharmacal Research, 2011. 34(4): p. 625-633.
8. WANG, J.P., Anti‐inflammatory Effect of Magnolol, Isolated from Magnolia officinalis, on A23187‐induced Pleurisy in Mice. Journal of Pharmacy and Pharmacology, 1995. 47(10): p. 857-860.
9. Joe, B., M. Vijaykumar, and B.R. Lokesh, Biological Properties of Curcumin-Cellular and Molecular Mechanisms of Action. Critical Reviews in Food Science and Nutrition, 2004. 44(2): p. 97-111.
10. Joe, B. and B. Lokesh, Role of capsaicin, curcumin and dietary n—3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1994. 1224(2): p. 255-263.
11. Joe, B. and B. Lokesh, Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages. Lipids, 1997. 32(11): p. 1173-1180.
12. Menon, V.P. and A.R. Sudheer, Antioxidant and anti-inflammatory properties of curcumin. Advances in Experimental Medicine and Biology 595:105-25 p.0065-2598 .
13. Radhakrishna Pillai, G., Induction of apoptosis in human lung cancer cells by curcumin. Cancer Letters, 2004. 208(2): p. 163-170.
14. Buhrmann, C., Significant decrease in the viability and tumor stem cell marker expression in tumor cell lines treated with curcumin. Journal of Herbal Medicine, 2020: p. 100339.
15. Anand, P., Bioavailability of curcumin: problems and promises. Molecular pharmaceutics, 2007. 4(6): p. 807-818.
16. Gao, S. and M. Hu, Bioavailability challenges associated with development of anti-cancer phenolics. Mini Reviews in Medicinal Chemistry, 2010. 10(6): p. 550-567.
17. González Canga, A., The pharmacokinetics and metabolism of ivermectin in domestic animal species. The Veterinary Journal, 2009. 179(1): p. 25-37.
18. Yang, S.C., Polyketal Copolymers: A New Acid-Sensitive Delivery Vehicle for Treating Acute Inflammatory Diseases. Bioconjugate Chemistry, 2008. 19(6): p. 1164-1169.
19. Fiore, V.F., Polyketal microparticles for therapeutic delivery to the lung. Biomaterials, 2010. 31(5): p. 810-817.
20. Patil, J.S. and S. Sarasija, Pulmonary drug delivery strategies: A concise, systematic review. Lung India : Official Organ of Indian Chest Society, 2012. 29(1): p. 44-49.
21. Bignold, L.P., Principles of Tumors: A Translational Approach to Foundations. Elsevier Science. 2019
22. Forouzanfar, M.H., Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The lancet, 2016. 388(10053): p. 1659-1724.
23. 臺灣衛生福利部統計處, 2020-06.
24. Barta, J.A., C.A. Powell, and J.P. Wisnivesky, Global Epidemiology of Lung Cancer. Annals of Global Health, 2019. 85(1): p. 8.
25. Nykamp, V., Surgical treatment of non-small cell lung cancer. South Dakota Medicine, 2010.
26. Sato, T., Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors. Molecular Cancer Therapeutics, 2015. 14(10): p. 2198.
27. Giard, D.J., In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. Journal of The National Cancer Institute, 1973. 51(5): p. 1417-1423.
28. Balis, J.U., Synthesis of lung surfactant-associated glycoproteins by A549 cells: description of an in vitro model for human type II cell dysfunction. Experimental Lung Research, 1984. 6(3-4): p. 197-213.
29. Lieber, M., A continuous tumor‐cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. International Journal of Cancer, 1976. 17(1): p. 62-70.
30. Nardone, L.L. and S.B. Andrews, Cell line A549 as a model of the type II pneumocyte: Phospholipid biosynthesis from native and organometallic precursors. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, 1979. 573(2): p. 276-295.
31. Shapiro, D.L., Phospholipid biosynthesis and secretion by a cell line (A549) which resembles type II alveolar epithelial cells. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1978. 530(2): p. 197-207.
32. Cox, Megan C., et al. "Toward the broad adoption of 3D tumor models in the cancer drug pipeline." ACS Biomaterials Science & Engineering 1.10 (2015): 877-894.
33. Langhans, Sigrid A. “Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning.” Frontiers in pharmacology vol. 9 6. 23 Jan. 2018, doi:10.3389/fphar.2018.00006
34. Birgersdotter, Anna, Rickard Sandberg, and Ingemar Ernberg. "Gene expression perturbation in vitro—a growing case for three-dimensional (3D) culture systems." Seminars in cancer biology. Vol. 15. No. 5. Academic Press, 2005.
35. Van Trinh, Ngu, et al. "Taraxacum officinale dandelion extracts efficiently inhibited the breast cancer stem cell proliferation." Biomedical Research and Therapy 3.7 (2016): 1-13.
36. Saltzman, WM., Drug delivery: Engineering principles for drug therapy. Oxford University Press. 2001
37. Patton, J.S. and P.R. Byron, Inhaling medicines: delivering drugs to the body through the lungs. Nature Reviews Drug Discovery, 2007. 6(1): p. 67-74.
38. Fanucchi, M.V., Pulmonary cytochrome P450 monooxygenase and Clara cell differentiation in mice. American Journal of Respiratory Cell and Molecular Biology, 1997. 17(3): p. 302-314.
39. Keith, I.M., Immunological identification and effects of 3-methylcholanthrene and phenobarbital on rat pulmonary cytochrome P-450. Cancer Research, 1987. 47(7): p. 1878-1882.
40. Tronde, A., Pulmonary absorption rate and bioavailability of drugs in vivo in rats: structure–absorption relationships and physicochemical profiling of inhaled drugs. Journal of Pharmaceutical Sciences, 2003. 92(6): p. 1216-1233.
41. Borghardt, J.M., C. Kloft, and A. Sharma, Inhaled Therapy in Respiratory Disease: The Complex Interplay of Pulmonary Kinetic Processes. Canadian Respiratory Journal, 2018: p. 2732017.
42. Labiris, N. and M. Dolovich, Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. British Journal of Clinical Pharmacology, 2003. 56(6): p. 588-599.
43. Tsuda, A., F.S. Henry, and J.P. Butler, Particle transport and deposition: basic physics of particle kinetics. Comprehensive Physiology, 2011. 3(4): p. 1437-1471.
44. Edsbäcker, S. and C.J. Johansson, Airway selectivity: an update of pharmacokinetic factors affecting local and systemic disposition of inhaled steroids. Basic & Clinical Pharmacology & Toxicology, 2006. 98(6): p. 523-536.
45. Sheth, P., S.W. Stein, and P.B. Myrdal, Factors influencing aerodynamic particle size distribution of suspension pressurized metered dose inhalers. Aaps Pharmscitech, 2015. 16(1): p. 192-201.
46. Rogueda, P.G. and D. Traini, The nanoscale in pulmonary delivery. Part 2: formulation platforms. Expert Opinion on Drug Delivery, 2007. 4(6): p. 607-620.
47. Heffernan, M.J. and N. Murthy, Polyketal Nanoparticles:  A New pH-Sensitive Biodegradable Drug Delivery Vehicle. Bioconjugate Chemistry, 2005. 16(6): p. 1340-1342.
48. Wang, Y., B. Chang, and W. Yang, pH-sensitive polyketal nanoparticles for drug delivery. Journal of Nanoscience and Nanotechnology, 2012. 12(11): p. 8266-8275.
49. Zhu, L., Characterization of Hepatic and Intestinal Glucuronidation of Magnolol: Application of the Relative Activity Factor Approach to Decipher the Contributions of Multiple UDP-Glucuronosyltransferase Isoforms. Drug Metabolism and Disposition, 2012. 40(3): p. 529.
50. Reddy, R.C., Deactivation of murine alveolar macrophages by peroxisome proliferator-activated receptor-γ ligands. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2004. 286(3): p. L613-L619.
51. Shen, P., Magnolol treatment attenuates dextran sulphate sodium-induced murine experimental colitis by regulating inflammation and mucosal damage. Life Sciences, 2018. 196: p. 69-76.
52. Park, J., In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. European Journal of Pharmacology, 2004. 496(1): p. 189-195.
53. Parray, H.A., Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes. Nutrition, 2018. 50: p. 82-90.
54. Shen, J., Magnolol inhibits the growth of non-small cell lung cancer via inhibiting microtubule polymerization. Cellular Physiology and Biochemistry, 2017. 42(5): p. 1789-1801.
55. Rasul, A., Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways. International Journal of Oncology, 2012. 40(4): p. 1153-1161.
56. Chen, J.-H., Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine. Toxicology and Applied Pharmacology, 2014. 279(3): p. 294-302.
57. Karki, R., O.-M. Ho, and D.-W. Kim, Magnolol attenuates neointima formation by inducing cell cycle arrest via inhibition of ERK1/2 and NF-κB activation in vascular smooth muscle cells. Biochimica et Biophysica Acta (BBA) - General Subjects, 2013. 1830(3): p. 2619-2628.
58. Chen, J.-S., Magnolol stimulates lipolysis in lipid-laden RAW 264.7 macrophages. Journal of Cellular Biochemistry, 2005. 94(5): p. 1028-1037.
59. Tsai, T., Protective effect of magnolol-loaded polyketal microparticles on lipopolysaccharide-induced acute lung injury in rats. Journal of Microencapsulation, 2016. 33(5): p. 401-411.
60. Menon, V.P. and A.R. Sudheer, Antioxidant And Anti-Inflammatory Properties Of Curcumin, in The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer US: Boston, MA. 2007, p. 105-125.
61. Lestari, M.L. and G. Indrayanto, Curcumin, in Profiles of drug substances, excipients and related methodology. Elsevier. 2014,p. 113-204.
62. Reddy, R.C., Curcumin for malaria therapy. Biochemical and Biophysical Research Communications, 2005. 326(2): p. 472-474.
63. Mahady, G.B., Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Research, 2002. 22(6C): p. 4179-4181.
64. E Wright, L., Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer. Current Pharmaceutical Design, 2013. 19(34): p. 6218-6225.
65. Aggarwal, B.B. and K.B. Harikumar, Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The International Journal of Biochemistry & Cell Biology, 2009. 41(1): p. 40-59.
66. Tsai, J.-R., Curcumin inhibits non-small cell lung cancer cells metastasis through the Adiponectin/NF-κb/MMPs signaling pathway. PLoS One, 2015. 10(12): p. e0144462.
67. Prasad, S., A.K. Tyagi, and B.B. Aggarwal, Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Research and Treatment : Official Journal of Korean Cancer Association, 2014. 46(1): p. 2-18.
68. Hasan, M., Liposome encapsulation of curcumin: physico-chemical characterizations and effects on MCF7 cancer cell proliferation. International Journal of Pharmaceutics, 2014. 461(1-2): p. 519-528.
69. Caly, L., The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research, 2020. 178: p. 104787.
70. Markowska, A., Doxycycline, salinomycin, monensin and ivermectin repositioned as cancer drugs. Bioorganic & Medicinal Chemistry Letters, 2019. 29(13): p. 1549-1554.
71. Juarez, M., A. Schcolnik-Cabrera, and A. Dueñas-Gonzalez, The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. American Journal of Cancer Research, 2018. 8(2): p. 317-331.
72. Gamboa, G.U., et al., Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications. Parasitology Research, 2016. 115(5): p. 1945-1953.
73. Clark, S.L., Long-term delivery of ivermectin by use of poly (D, L-lactic-co-glycolic) acid microparticles in dogs. American Journal of Veterinary Research, 2004. 65(6): p. 752-757.
74. Lee, S., Polyketal microparticles: a new delivery vehicle for superoxide dismutase. Bioconjugate Chemistry, 2007. 18(1): p. 4-7.
75. Corrigan, O.I. and X. Li, Quantifying drug release from PLGA nanoparticulates. European Journal of Pharmaceutical Sciences, 2009. 37(3): p. 477-485.
76. Sakamoto Sasaki, S., Components of Turmeric Oleoresin Preparations and Photo-stability of Curcumin. Japanese Journal of Food Chemistry and Safety, 1998. 5(1): p. 57-63.
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