Responsive image
博碩士論文 etd-1104117-095444 詳細資訊
Title page for etd-1104117-095444
論文名稱
Title
超音波乳化製備聚己內酯微球於藥物載體
Preparation of polycaprolactone microspheres for drug carrier by ultrasonic emulsification
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
71
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2017-07-24
繳交日期
Date of Submission
2017-12-04
關鍵字
Keywords
PCL微球、乳化法、均勻設計實驗法、細胞毒性測試、藥物載體
Emulsion process, PCL microspheres, Uniform design experiment method, Leukemia test, Drug carrier
統計
Statistics
本論文已被瀏覽 5685 次,被下載 0
The thesis/dissertation has been browsed 5685 times, has been downloaded 0 times.
中文摘要
本研究以超音波噴頭結合乳化方式 (Emulsion process),經由高分子材料聚己內酯 (Polycaprolactone, PCL) 製備出高粒徑均勻度之功能性微載體。PCL具有良好的生物降解性 (Biodegradability) 、生物相容性 (Biocompatibility) 、低熔點及高結晶性等特性,非常適合做於藥物之載體,研究過程藉由功率、幫浦進給速率、磁石轉速、聚乙烯醇 (Polyvinylalcohol, PVA) 濃度、PVA溶液溫度以及液滴滴落距離六種不同的參數,結合均勻設計實驗法 (Uniform design experimentation) 探討在不同的實驗條件下,微載體粒徑分佈的範圍及均一性,主要透過進給幫浦將PCL溶液以等速方式輸出至超音波噴頭,利用超音波噴頭表面所產生的駐波,將PCL溶液以液滴的方式滴落至下方PVA溶液,並在PVA溶液中加入磁石進行攪拌,使得PCL溶液析出溶液,產生PCL微載體,透過UV分光光譜儀建立檢量線,進而量測載藥率、包覆率、降解率以及釋放率,研究結果表示在PCL溶液濃度11.5 wt%、功率12.1 W、幫浦進給速率1.42 ml/min、磁石轉速690 rpm、PVA溶液濃度 13.3 wt%、PVA溶液溫度49 oC以及液滴滴落距離36.16 mm的參數下,可以製備出66.66 %均勻度,粒徑範圍約在30~50 μm之球狀載體,此載體之載藥率為7.265 %、包覆率為23.685%、釋放率在48小時達到2.1 %、降解率呈非線性在第14天時可達到80 %。
Abstract
In this study, functional Polycaprolactone (PCL) microcarriers with high uniformity of particle size are prepared by ultrasonic nozzles. PCL has some good property for carrier of drug such as biodegradability, biocompatibility, low melting point and high crystallinity. Power, pump feeding rate, magnet rotation speed, the concentration of Polyvinylalcohol (PVA) solution, temperature, and droplet distance are the parameter used in the study. The range of particle size under different experimental condition is investigated by the uniform design experiment. PCL solution is delivered to the nozzle with constant speed by the infusion pump. Then PCL solution is sprayed into PVA solution by using the standing wave on the surface of ultrasonic nozzle. PVA solution stirred with magnet to separate out the microcarrier. The drug loading rate, coating rate, degradation rate, and release rate with the UV spectrophotometer was obtained. The results show that the size of microcarrier particle between 30 to 50 μm are produced by the parameters of PCL solution when the concentration is 11.5 wt%, power is 12.1 W, pump feeding rate is 1.42 ml/min, magnet speed is 690 rpm, PVA solution concentration is 13.3 wt%, temperature is 49 oC, and collecting distance is 24 mm. The uniformity of the microcarrier is 66.66% was obtained by above condition. And the drug loading rate is 7.265%, the coating rate is 23.685%, the degradation rate is reached to 80% at 14 days, and the release rate is reached to 2.1% at 48 hours.
目次 Table of Contents
第一章 緒論 5
1.1前言 5
1.2研究背景與動機 5
1.3研究目的 6
1.4本文架構 6
第二章 文獻回顧 7
2.1高分子材料-聚己內酯 (PCL) 7
2.2超音波噴頭 8
2.3高分子微球製程 10
2.4藥物載體應用 12
2.5生物降解 14
第三章 研究方法與步驟 19
3.1實驗流程架構 19
3.2實驗藥品與設備 19
3.3實驗製程 20
3.3.1乳化法溶液配置 20
3.3.2超音波乳化法製備 21
3.4均勻設計實驗法 22
3.4.1均勻設計表 22
3.4.2均勻實驗程序 25
3.4.3均勻設計實驗結果分析 25
3.5微載體特性量測 26
3.5.1檢量線建立 27
3.5.2載藥率量測 28
3.5.3包覆率量測 29
3.5.4釋放率量測 30
3.5.5降解率量測 30
3.6實驗分析儀器介紹 31
3.6.1流變儀 31
3.6.2掃描式電子顯微鏡 32
3.6.3表面張力量測儀 33
3.6.4 UV分光光譜儀 33
第四章 實驗結果與討論 35
4.1均勻設計實驗法分析 35
4.1.1均勻設計實驗法分析之PCL微球粒徑百分比 35
4.1.2均勻實驗設計法-線性回歸 45
4.1.3超音波乳化法PCL微載體製程參數最佳化分析 45
4.1.4最佳化參數之超音波乳化法PCL微球製程 46
4.2微載體特性量測結果分析 47
4.2.1載藥率及包覆率比較 47
4.2.2釋放率比較 50
4.2.3降解率比較 58
第五章 結論與未來展望 62
5.1結論 62
5.2未來展望 63
參考文獻 64
參考文獻 References
[1] 林雅婷, “奈米國家型科技計畫生醫領域研發成果,” 台灣奈米會刊, 2014.
[2] Severian Dumitriu and Marcel Dekker, “In Polymeric Biomaterials,” New York, 1994.
[3] 潘勁屹, “聚己內酯表面活化與表面奈米化對細胞生長之研究,” 碩士論文,化學工程系, 國立雲林科技大學, 2004.
[4] 王基信, “以電氣紡絲法製備PLA/PCL小管徑人工血管支架之性質及其細胞生長研究,” 碩士論文, 機械工程系, 國立交通大學, 2012.
[5] 蔡佩琳, “電紡絲聚己內酯多元醇(PCL)纖維支架中纖維特性對細胞貼附與增生影響之研究,” 碩士論文, 工程科技研究所, 私立萬能科技大學, 2010.
[6] K. D. P. D. K. Han, S. Y. Jeong, Y. H. Kim, U. Y. Kim, and B. G. Min, “In-Vivo Biostability and Calcification-Resistance of Surface-Modified Pu-Peo-So3,” Journal of Biomedical Materials Research, vol. 27, pp. 1063-1073, 1993.
[7] J. M. Anderson, A. Rodriguez, and D. T. Chang, “Foreign body reaction to biomaterials,” Seminars in Immunology, vol. 20, pp. 86-100, Apr 2008.
[8] J. W. H. Frank J. van Natta, Wallace H. Carothers, “Studies of Polymerization and Ring Formation. XXIII.1 ε-Caprolactone and its Polymers,” J. Am. Chem. Soc., vol. 56, pp. 455-457, 1934.
[9] Van Natta F J, Hill J W, C. W, and H. F. Mark, “Polymerization and ring formation ε-caprolactone and its polymers,” J Am Chem Soc, vol. 56, pp. 455-459, 1934.
[10] R. Chandra and R. Rustgi, “Biodegradable polymers,” Progress in Polymer Science, vol. 23, pp. 1273-1335, 1998.
[11] L. S. Nair and C. T. Laurencin, “Biodegradable polymers as biomaterials,” Progress in Polymer Science, vol. 32, pp. 762-798, 2007.
[12] H. T., “Biodegradable polymers for biomedical uses,” Progr Polym Sci, vol. 19, pp. 663-702, 1994.
[13] M. A. Woodruff and D. W. Hutmacher, “The return of a forgotten polymer—Polycaprolactone in the 21st century,” Progress in Polymer Science, vol. 35, pp. 1217-1256, 2010/10/01/ 2010.
[14] C. Choong, J. T. Triffitt, and Z. F. Cui, “Polycaprolactone Scaffolds for Bone Tissue Engineering,” Food and Bioproducts Processing, vol. 82, pp. 117-125, 2004.
[15] E. J. Chong, T. T. Phan, I. J. Lim, Y. Z. Zhang, B. H. Bay, S. Ramakrishna, et al., “Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution,” Acta Biomaterialia, vol. 3, pp. 321-330, 2007.
[16] R. J. Lang, “Ultrasonic Atomization of Liquids,” The acoustical society of america, vol. 34, 1962.
[17] K. P. Yoon Yeo, “A new microencapsulation method using an ultrasonic atomizer based on interfacial solvent exchange,” Controlled Release, vol. 100, pp. 379-388, 2004.
[18] 鄭義忠, 王唯帆, 李偉雄, 孫長春, and 胡文華, “影響次微米高分子微球製備因素之探討,” 中正嶺學報, vol. 34, 2005.
[19] G. Odian, “In Principles of polymerization, 3rd ed.,” Wiley-Interscience: NewYork, 1991.
[20] Barrett and K.E.J, “In Dispersion polymerization in encyclopedia of polymer science and engineering,” Wiley: Chichester, UK, 1975.
[21] 郭育丞, “快速合成均一粒徑功能性次微米球及其應用,” 化學工程與材料工程學系, 國立中央大學, 2013.
[22] H. F. Mark, N. M. Bikales, C. G. Overberger, and G. Menges, “In Encyclopedia of polymer science and engineering, 2nd ed.,” John Wiley & Sons, Inc.: New York, vol. 17, p. 321, 1985.
[23] E. Allemann, R. Gurny, and E. Doelker, “DRUG-LOADED NANOPARTICLES - PREPARATION METHODS AND DRUG TARGETING ISSUES,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 39, pp. 173-191, Oct 1993.
[24] K. K. K. Cory Berkland , Daniel W. Pack*, “Fabrication of PLG microspheres with precisely controlled and monodisperse size distributions,” Journal of Controlled Release, vol. 73, pp. 59-74, 2001.
[25] P. Giunchedi, B. Conti, L. Maggi, and U. Conte, “CELLULOSE-ACETATE BUTYRATE AND POLYCAPROLACTONE FOR KETOPROFEN SPRAY-DRIED MICROSPHERE PREPARATION,” Journal of Microencapsulation, vol. 11, pp. 381-393, Jul-Aug 1994.
[26] H. C. Maa YF1, “Effect of primary emulsions on microsphere size and protein-loading in the double emulsion process.,” J Microencapsul., vol. 14, pp. 225-41, 1997.
[27] C. D. Trotta M1, Cavalli R, Peira E., “Hydrophilic microspheres from water-in-oil emulsions by the water diffusion technique.,” Pharm Res, vol. 21, pp. 1455-9, 2004.
[28] N. Oku, Y. Namba, and S. Okada, “TUMOR ACCUMULATION OF NOVEL RES-AVOIDING LIPOSOMES,” Biochimica Et Biophysica Acta, vol. 1126, pp. 255-260, Jun 1992.
[29] 國立台灣大學醫學院附設醫院, “經動脈灌流化學栓塞治療(Transarterial Chemoembolization, TACE),” 2015.
[30] P. D. Varde NK1, “Microspheres for controlled release drug delivery.,” Expert Opin Biol Ther, vol. 4, pp. 35-51, 2004.
[31] S. Freiberg and X. X. Zhu, “Polymer microspheres for controlled drug release,” International Journal of Pharmaceutics, vol. 282, pp. 1-18, 2004.
[32] YUTAKA TOKIWA and T. SUZUKI, “Hydrolysis of polyesters by lipases,” Nature, vol. 270, pp. 76-78, 1977.
[33] H.-H. Lee, H.-S. Yu, J.-H. Jang, and H.-W. Kim, “Bioactivity improvement of poly(ε-caprolactone) membrane with the addition of nanofibrous bioactive glass,” Acta Biomaterialia, vol. 4, pp. 622-629, 2008.
[34] S. Lenoir , R. Riva , X. Lou , Ch. Detrembleur , R. Jérôme , and P. Lecomte, “Ring-Opening Polymerization of α-Chloro-ε-caprolactone and Chemical Modification of Poly(α-chloro-ε-caprolactone) by Atom Transfer Radical Processes,” Macromolecules, vol. 37, pp. 4055-4061, 2004.
[35] Raphaël Riva , Stéphanie Schmeits , Christine Jérôme , Robert Jérôme , and P. Lecomte, “Combination of Ring-Opening Polymerization and “Click Chemistry”:  Toward Functionalization and Grafting of Poly(ε-caprolactone),” Macromolecules, vol. 40, pp. 796-803, 2007.
[36] R. LANGER, “INVITED REVIEW POLYMERIC DELIVERY SYSTEMS FOR CONTROLLED DRUG RELEASE,” Chemical Engineering Communications, vol. 6, pp. 1-48, 1980.
[37] A. Göpferich, “Mechanisms of polymer degradation and erosion,” Biomaterials, vol. 17, pp. 103-114, 1996.
[38] Johnna S. Temenoff and A. G. Mikos, “Biomaterials: The Intersection of Biology and Materials Science,” Pearson/Prentice Hall: USA, 2008.
[39] J.-C. Leroux, E. Allémann, F. De Jaeghere, E. Doelker, and R. Gurny, “Biodegradable nanoparticles — From sustained release formulations to improved site specific drug delivery,” Journal of Controlled Release, vol. 39, pp. 339-350, 1996/05/01/ 1996.
[40] J. O. and Hollinger, “Biomedical Applications of Synthetic Biodegradable Polymers,” CRC Press: USA, 1995.
[41] 黃啟豪, “The preparation of micro-sphere polycaprolactone for bio-application by emulsion process,” 碩士論文, 機械與機電工程研究所, 國立中山大學, 2016.
[42] S. N. L. Hans Bruun Nielsen, Jacob Søndergaard, “DACE ‒ A MATLAB kriging toolbox,” DTU: Denmark, 2002.
[43] Y.-F. Shih and T.-M. Wu, “Enzymatic degradation kinetics of poly(butylene succinate) nanocomposites,” Journal of Polymer Research, vol. 16, pp. 109-115, 2009.
[44] H.-K. Fu, S.-W. Kuo, C.-F. Huang, F.-C. Chang, and H.-C. Lin, “Preparation of the stimuli-responsive ZnS/PNIPAM hollow spheres,” Polymer, vol. 50, pp. 1246-1250, 2009.
電子全文 Fulltext
本電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。
論文使用權限 Thesis access permission:自定論文開放時間 user define
開放時間 Available:
校內 Campus:永不公開 not available
校外 Off-campus:永不公開 not available

您的 IP(校外) 位址是 3.22.248.208
論文開放下載的時間是 校外不公開

Your IP address is 3.22.248.208
This thesis will be available to you on Indicate off-campus access is not available.

紙本論文 Printed copies
紙本論文的公開資訊在102學年度以後相對較為完整。如果需要查詢101學年度以前的紙本論文公開資訊,請聯繫圖資處紙本論文服務櫃台。如有不便之處敬請見諒。
開放時間 available 永不公開 not available

QR Code