![]() |
|
以作者查詢圖書館館藏 、以作者查詢臺灣博碩士 、以作者查詢全國書目 、勘誤回報 、線上人數:44 、訪客IP:13.58.24.13
姓名 林宜美(Yi-Mei Lin) 查詢紙本館藏 畢業系所 化學工程與材料工程學系 論文名稱 幾丁質摻合聚乳酸酯微粒於藥物釋放系統之研究
(Chitin/PLGA blend microspheres as a biodegradable drug delivery system: Phase separation, degradation and release behavior)相關論文 檔案 [Endnote RIS 格式]
[Bibtex 格式]
[相關文章]
[文章引用]
[完整記錄]
[館藏目錄]
[檢視]
[下載]
- 本電子論文使用權限為同意立即開放。
- 已達開放權限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。
摘要(中) 中 文 摘要
本研究主要的目的是利用溼式相轉化製程來製備幾丁質(chitin)摻合聚乳酸酯(PLGA)之藥物載體微小球,並以改變重量比例、水相溫度及聚乳酸酯中乳酸/羥基乙酸共聚比例不同等條件來形成不同系列的微小球。本研究藉由水含量實驗掃描式電子顯微鏡(SEM) 、示差掃描熱卡計(DSC) 、X-ray粉末繞射儀(XRD) 、霍氏紅外線光譜儀(FTIR)的分析以及來探討此微小球的基本物性及表面結構型態,並經由體外裂解實驗來觀察此載體裂解的速率與行為。
由SEM觀察可得,幾丁質/聚乳酸酯摻合微小球中有許多聚乳酸酯微小顆粒散佈在幾丁質基質中,顯示摻合微小球中幾丁質與聚乳酸酯呈現微相分離的情形。當改變製程中水相溫度時,聚乳酸酯在微小球中均勻分散的程度會隨著溫度的增加而增加,顯示提高製程溫度可增加幾丁質與聚乳酸酯的摻合性。在體外裂解實驗中,微小球的重量損失隨著幾丁質含量增加以及聚乳酸酯中羥基乙酸比例增加而增加。根據SEM和DSC的分析結果可知,幾丁質/聚乳酸酯摻合微小球的裂解作用是藉由幾丁質表面的剝蝕效應和聚乳酸酯的整體溶蝕水解而進行。幾丁質/聚乳酸酯以不同重量比摻合的微小球包覆抗癌藥物進行藥物釋放,其釋放曲線呈現兩階段的釋放模式,初期為快速且大量的釋放,且隨著幾丁質含量增加而釋放速率增加,後期釋放速率緩慢且可延續釋放至7天以上。不同溫度製程系列和不同共聚比例之聚乳酸酯系列的幾丁質/聚乳酸酯摻合微小球包覆蛋白質進行釋放,隨著其釋放曲線也呈現兩階段釋放行為,而初期為緩慢的釋放,且隨著製程溫度升高其釋放速率較快,而聚乳酸酯共聚合物比例也會影響蛋白質的釋放速率,後期則為大量且快速的釋放,整體的釋放情形可持續釋放至14天以上。摘要(英) Abstract
A novel chitin-based microsphere was developed for drug-delivery purpose in the present study. These biodegradable microspheres were prepared by directly blending chitin with poly(D,L-lactide-co-glycolide ) (PLGA) in DMAc-LiCl solution, followed by being coagulated in water via wet phase inversion. Three condition of the experiment were employed:chitin has blended with different contents of PLGA, and blending solution has been coagulated in water with different temperature, and chitin has blended with different copolymer composition ratio of PLGA. The physicochemical properties of chitin/PLGA blend microspheres were studied by water uptake capacity, in vitro degradation test, SEM, DSC, XRD, and FTIR.
SEM micrography of the blend microsphere showed that there are numerous PLGA particulates homogeneously dispersed in chitin matrix, suggesting the occurrence of obvious phase separation from the blended chitin and PLGA phase. The distribution of PLGA in chitin matrix has been improved by higher water temperature. From SEM observed, the well-distributed properties of PLGA in chitin/PLGA microspheres were increased with higher water temperature. Weight loss of the chitin/PLGA blend microsphere increases with the increase of chitin content in the microsphere, and also increases with the increase of glycolide composition ratio of PLGA. Degradation of the chitin/PLGA blend microsphere depends on the surface erosion of chitin phase and bulk hydrolysis of PLGA phase, according to the examinations of SEM and DSC studies. Two-phase drug release model is observed from the release of chlorambucil from chitin/PLGA blend microspheres. The initial stage of fast drug-release rate increases with the increased chitin content, the followed stage of slow release is sustained for several days. However, the release of Albumin from chitin/PLGA blend microspheres in different water temperature series and different copolymer ratio of PLGA series also have two-stage release model, but the initial stage has slowly release rate that increases with raising water temperature during preparing process, and the different copolymer composition ratio of PLGA also has effect on the protein release rate; the followed stage has fast release rate and sustained for 14 days.關鍵字(中) ★ 幾丁質
★ 聚乳酸酯
★ 乳酸羥基乙酸共聚合物
★ 藥物釋放關鍵字(英) ★ L-lactide-co-glycolide)
★ chitin
★ PLGA
★ Poly(D
★ drug-release論文目次 目 錄
目錄……………………………………………………………………..Ⅰ
表目錄……………………………………………………………….….Ⅲ
圖目錄……………………………………………………………….….Ⅳ
中文摘要…………………………………………………………….….Ⅷ
英文摘要…………………………………………………………….….Ⅸ
第一章 緒論…………………………………………………………..1
第二章 文獻回顧……………………………………………………..3
2.1 藥物控制釋放…………………………………………………….3
2.1.1 微粒包覆技術………………………………………………..7
2.2 幾丁質……………………………………………………………..7
2.2.1 幾丁質的製備………………………………………………..10
2.2.2 幾丁質的物理與化學性質…………………………………..10
2.2.3 幾丁質在生醫材料上的特性及應用………………………..11
2.3 聚乳酸(PLA)與乳酸/羥基乙酸共聚合高分子(PLGA)………….14
2.3.1 PLA與PLGA的合成………………………………………..18
2.3.2 PLA與PLGA的物理性質與水解作用………………………18
2.3.3 PLA與PLGA之生物相容性………………………………….23
2.3.4 PLA與PLGA生醫材料上之研究與應用…………………….23
2.4 抗癌樂物chlorambucil……………………………………………..24
2.5 牛血清白蛋白(BSA)……………………………………………….25
2.6 濕式相轉化法……………………………………………………...26
第三章 實驗……………………………………………………………30
3.1 實驗目的…………………………………………………………30
3.2 實驗藥品…………………………………………………………..30
3.3 實驗儀器…………………………………………………………..31
3.4實驗方法……………………………………………………………31
3.4.1 Chitin與PLGA摻合微小球之製備…………………………..33
3.4.2 包覆藥物之Chitin/PLGA摻合微小球之製備……………….34
3.4.3 掃描式電子顯微鏡(SEM)表面結構觀察…………………….34
3.4.4 紅外線光譜分析(FTIR)實驗………………………………….35
3.4.5 微差掃描式熱分析(DSC)實驗………………………………..35
3.4.6 X-ray光譜分析(XRD)實驗……………………………………35
3.4.7 水含量實驗……………………………………………………35
3.4.8 體外裂解(in vitro)實驗……………………………………….36
3.4.9 藥物釋放實驗…………………………………………………36
3.4.10 蛋白質釋放實驗……………………………………………..36
第四章 結果與討論……………………………………………………37
4.1 SEM表面結構觀察分析…………………………………………..37
4.2 DSC分析…………………………………………………………...49
4.3 XRD分析…………………………………………………………..55
4.4 FTIR分析…………………………………………………………..60
4.5 水含量分析………………………………………………………..64
4.6 體外裂解實驗分析………………………………………………66
4.7 藥物釋放分析……………………………………………………77
4.8 蛋白質釋放分析…………………………………………………..83
第五章 結論……………………………………………………………95
參考文獻 ………………………………………………………………97參考文獻 參考文獻
1. Rom E.Eliaz, Joseph Kost, J. Biomed. Materi. Res., vol.50, pp388, 2000.
2. Park TC, Cohen S, Langer R, Macromolecules., vol.25, pp116, 1992.
3. Ibim SEM, Ambrosio AMA, Kwon MS, El-Amin SF, Allcock HR, Laurencin CT. Biomaterials., vol.18, pp1565, 1997.
4. Pitt CG, Cha Y, Shah SS, Zhu KJ. J. Control. Release., vol.19, pp189, 1992.
5. P. K. Gupta, H. Johnson and C. Allexon, J. Control. Release., vol.26, pp229, 1993.
6. P. Beck, J. Kreuter and I. Fichtner, J. Microencapsul., vol.10, pp101, 1993.
7. P. B. Deasy, Marcel Dekker Inc., pp8-13, 1984.
8. R. Jalil and J. R. Nixon, J. Microencapsul., vol.41, pp473, 1989.
9. R. Bodmeier and H. Chen, J. Pharm. Pharmacol., vol.40, pp754, 1988.
10. R. S. Harland, C. Dubernet, J. P. Bennit and N. A. Peppas, J. Control. Release., vol.7, pp207, 1988.
11. H. Simpson and I. Mc Kinlay, Brit. Med. J., vol.4, pp462, 1975.
12. 吳柏昇,丁醯化殼聚醣及其與聚乳酸摻合物之研究,成功大學化學工程研究所論文,民國89年6月
13. 簡永浩,幾丁聚醣之發酵製程與規模放大,清華大學化學工程研究所論文,民國八十九年六月
14. 林美葉,生物資源-生物技術,vol.2, pp29, 2000.
15. Klokkevold, P. R., Vandemark, L., kenney E. B., and Bermard, G. W., J. Peri-odont., vol.67, pp1170, 1996.
16. 傅佑璋,聚乳酸(PLA)及乳酸/羥基乙酸(PLGA)共聚合物於抗癌藥物傳輸系統之研究,中央大學化學工程研究所論文,民國89年6月
17. K. Masters, Spray Drying Handbook, 3rd ed., George Godwin, London, 1979.
18. J. M. Newton, Manuf. Chem., Aerosol News, vol.33, pp33, 1966.
19. 黃義侑,化工技術,vol.4, pp152, 1996
20. S. Cohen, M.J. Alonso, R. Langer, Int. J. Technol Assessment Health Care, vol.10, pp121, 1994.
21. C. G. Pitt, F. I. Chasalow, Y. M. Hibionada, D. M. Klimas and A. Schindler, J. Appl. Polym. Sci., vol.26, pp3779, 1981.
22. H. Fukuzaki, M. Yoshida, M. Asano and M. Kumakura, Eur. Polym. J., vol.25, pp 1019, 1989.
23. R. A. Miller, J. M. Brady, D. E. Cutright, J. Biomed. Materi. Res., vol.11, pp711, 1977.
24. E. J. Frazza and E. E. Schmitt, J. Biomed. Materi. Res. Symp., vol.1, pp43, 1971.
25. D. L. Hay, N. Cheegini and B. J. Masterson, J. Biomed. Materi. Res., vol.22, pp179, 1988.
26. R. Arshady, Biomaterials., Vol.14, pp5, 1993.
27. D. Shiaw-Guang Hu and Hsin-Jian Liu, Polym. Bull., vol.30, pp669-676, 1993.
28. G. J. Beumer, C.A. Van Blitterswijk, and M. Poneck, J. Biomed. Materi. Res., Vol.265, pp1277, 1992.
29. T. Tsuruts, Biomedical Application of Polymeric Materials, pp78, 1995.
30. M. Vert, G. Schwarch and J. Coudane, Pure. Appl. Chem., vol.32, pp787, 1995.
31. Anscomb, N. Hira and B. Hunt, Brist. J. Surgery, vol.57, pp917, 1970.
32. J. M. Brady, D. E. Cutright, R. A. Miller, G. C. Battistone and E. E. Hunsuck, J. Biomed. Materi. Res. , vol.7, pp155, 1973.
33. P. Christel, F. Chabot, J. L. Leray, C. Morin and M. Vert, Biomaterials., pp271, 1980.
34. E. J. Frazza and E. E. Schmitt, J. Biomed. Materi. Res. Symp., vol.1, pp43, 1971.
35. D. L. Hay, N. Cheegini and B. J. Masterson, J. Biomed. Materi. Res., vol.22, pp179, 1988.
36. Y. Ikada, J. Jpn. Soc. Adhesion., vol.6, pp17, 1980.
37. Y. Kimura and H. Kudo, J. Control. Release, vol.19, pp201, 1992.
38. Baras , M.-A. Benoit, J. Cillard, Int. J. Pharm., vol.200, pp133, 2000.
39. Rajeev and K. Janie, Biomaterials., vol.21, pp2475, 2000.
40. M. Vert, G. Schwarch and J. Coudane, Pure. Appl. Chem., vol.32, pp787, 1995.
41. S.Cohen, T. Yoshioka, M. Lucarelli, H. L. Hwang, R. Langer, Pharm. Res., vol.8, pp713, 1991.
42. Yamakawa, M. Kawahara, S. Watanabe, and Y. Miyake, J. Pharm. Sci., vol.79, pp505, 1990.
43. A. Eppstein, C. G. Kurahara, N.A. Bruno, M. A. Van Der Pas, Y. V. Marsh, and B. B. Schryver. Biology of the interferon system, Elsevier Science Publishers, pp401, 1986 .
44. J. C. Gautier, J. L. Grangier, A. Barbier, P. Dupont, D. Dussossoy, G. Pastor, and P. Couvreur, J. Control. Release, vol.20, pp67, 1992.
45. T. O’Hagan, D. Rahman, J. P. McGee, H. Jeffrey, M. C. Davies, P. Willians, S. S. Davis, and S. J. Challacombe, Immunology., vol.73, pp239, 1991.
46. T. Peters, Academic Press, pp161, 1985.
47. 糜福龍,幾丁聚醣應用於藥物及疫苗傳輸系統之設計及研究,中央大學化學工程研究所論文,民國86年4月
48. Angela G., Hausberger, Patrick P. Deluca, J. pharm. biomed. anal., Vol.13, pp.747, 1995.
49. Muzzarelli RAA, Carbohyd. Polym., vol.3, pp52, 1993.
50. Longdi Ren, Seiichi Tokura, Carbohyd. Polym., vol.23, pp.19, 1994.指導教授 徐新興(Shin-Shing Shyu) 審核日期 2002-7-3 推文 plurk
funp
live
udn
HD
myshare
netvibes
friend
youpush
delicious
baidu
網路書籤 Google bookmarks
del.icio.us
hemidemi
myshare