Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3151
標題: PLGA的化學改質與包覆抗精神疾病藥物olanzapine之製備及功效評估
Chemical Modification of Ploy(Lactic Acid-co-Glycolic Acid) and the Applications for Long-Term Drug Release of Olanzapine-Encapusulated Microspheres
作者: 藍裕臻
Lan, Yu-Chen
關鍵字: 共聚乳酸-甘醇酸;poly(lactide-co-glycolide) (PLGA);奧氮平;聚乙二醇;蔗糖;長效釋放;monomethoxy poly(ethylene glycol) (mPEG);sucrose;olanzapine;long-term sustained release
出版社: 化學工程學系所
引用: 1. A. K. Dash, G. C. 2nd Cudworth, J. Pharmacol Toxicol Methods,40 (1998) 1-12. 2. D. Lemoine, C. Francois, F. Kedzierewicz, V. Preat, M. Hoffman, P. Maincent, Biomaterials, 17 (1996) 2191-2197. 3. E. Fournier, C. Passirani, C. N. Montero-Menei, J. P. Benoit, Biomaterials, 24 (2003) 3311–3331. 4. S. J. Lee, Y. J. Park, S. N. Park, Y. M. Lee, Y. J. Seol, Y. Ku, C. P. Chung., J. Biomedical Mater Res., 55 (2001) 295–303. 5. R. E. Eliaz, J. Kost, J. Biomedical Mater Res., 50 (2000) 388–396. 6. T. M. Meese, Y. Hu, R. W. Nowak, K. G. Marra, J. Biomaterials Sci. Polym. Ed., 13 (2002) 141-151. 7. H. A. Recum, R. L. Cleek, E. G. Suzanne, A. G. Mikos, Biomaterials, 16 (1995) 441-447. 8. S. J. Holland, B. J. Tighe, P. L. Gould, J. Contr. Rel., 4 (1986) 155-180. 9. D. H. Lewis, M. Chasin, and R. Langer, Marcel Dekker, (1990) l-41 10. H. Shiaw-Guang, L. Hsin-Jian, Polym. Bull., 30 (1993) 669-676. 11. M. Dunne, O. I. Corrigan, Z. Ramtoola, Biomaterials, 21 (2000) 1659–1668. 12. J. Kang, S. P. Schwendeman, Biomaterials, 23 (2002) 239-245. 13. T. C. Park, S. Cohen, R. Langer, Macromolecules., 25 (1992) 116. 14. K. Alekha, C. Greggrey, J. Pharm. Toxicolog, 40 (1998) 1-12. 15. K. Fu, R. Harrell, K. Zinski, C. Um, A. Jaklenec, J. Frazier, N. Lotan, P. Burke, A. M. Klibanov, R. Langer, J. Pharm. Sci., 92 (2003) 1582-1591. 16. P. Homayoun, T. Mandal, D. Landry, H. Komiskey, J. Pharm. Pharmacol., 55 (2003) 933-938. 17. Aubert-Ppouessel, D. C. Bibby, M. C. Venier-Julienne, F. Hindre, J. P. Benoit, Pharm. Res., 19 (2002) 1046-1105. 18. V. G. Roullin, J. R. Deverre, L. Lemaire, F. Hindre, M. C. Venier-Julienne, R. Vienet, J. P. Benoit, Eur. J. Pharm. Biopharm., 53 (2002) 293-299. 19. J. Wang, B. M. Wang, S. P. Schwendeman, J. Control. Release, 82 (2002) 289-307. 20. M. Ramchandani, M. Pankaskie, D. Robinson, J. Control. Release, 43 (1997) 161-173. 21. T. K. Mandal, S. Pamujula, R. A. Graves, V. Kishore, Eur. J. Pharm. and Biopharm., 57 (2004) 213-218. 22. M. Chacon, J. Molpeceres, L. Berges, M. Guzman, M. R. Aberturas, Eur. J. Pharm. Sci., 8 (1999) 99-107. 23. Y. W. Tong, S. Q. Liu, Y. Y. Yang, Biomaterials, 26 (2005) 5064-5074. 24. T. H. Kim, H. Lee, T. G. Park, Biomaterials, 23 (2002) 2311-2317. 25. M. Cegnar, J. Kos, J. Kristl, Eur. J. Pharm. Sci., 22 (2004) 357-364. 26. M. Wolf, M. Wirth, F. Pittner, F. Gabor, Int. J.Pharm., 256 (2003) 141-152. 27. J. M. Ruis, J. P. Benoit, J. Control. Release, 16 (1991) 177-186. 28. M. Diwan, T. G. Park, J. Control. Release, 73 (2001) 223-244. 29. M. Igartua, R. M. Hernandez, A. Esquisabel, A. R. Gascon, M. B. Calvo, J. L. Pedraz, Int. J. Pharm., 169 (1998) 45-54. 30. J. Wang, B. M. Wang, S. P. Schwendeman, J. Control. Release, 82 (2002) 289-307. 31. J. L. Cleland, E. Duanes, A. Daugherty, M. Marian, J. Yang, M. Wilson, A. C. Celniker, A. Shahzamani, V. Quarmby, H. Chu, J. Control. Release, 49 (1997) 193-205. 32. M. Yokoyama, T. Okano, Y. Sakurai, A. Kikuchi, N. Ohsako, Y. Nagasaki, K. Kataoka, Bioconjugate Chem., 3 (1992) 275-276. 33. F. Bueckmann, M. Morr, G. Johansson, Makromol. Chem., 182 (1981) 1379-1384. 34. J. M. Harris, Macromol. Chem. Phys.C, 25 (1985) 325-373. 35. J. M. Harris, E. C. Struck, M. G. Case, M. S. Paley, M. Yalpani, J. M. Van Alstine, D. E. Brooks, J. Polym. Sci., 22 (1984) 341-352. 36. N. Topchieva, A. I. Kuzaev, V. P. Zubov, Eur. Polym. J., 24 (1988) 899-904. 37. Polson, G. M. Potgieter, J. F. Largier, G. E. Mears, J. F. Joubert, Biochim. Biophys. Acta, 82 (1964) 463-475. 38. M. Zeppezauer, S. Brishammar, Biochim. Biophys. Acta, 94 (1965) 581-583. 39. P. W. Chun, M. Fried, E. E. Ellis, Anal. Biochem., 19 (1967) 481-497. 40. P. A. Albertsson,“Partition of Cell Particles and Macromolecules”, 3rd edition, Wiley New York, (1986). 41. Abuchowski, T. Van Es, N. C. Palczuk, F. F. Davis, J. Biol. Chem., 252 (1977) 3578-3581. 42. E. Hurwitz, L. N. Klapper, M. Wilchek, Y. Yarden, M. Sela, Cancer Immunol. Immu., 49 (2000) 226-234. 43. Abuchowski, T. Van Es, N. C. Palczuk, F. F. Davis, J. Biol. Chem., 252 (1977) 3578-3581. 44. F. M. Veronese, Biomaterials, 22 (2001) 405-417. 45. R. A. Scott, N. A. Peppas, Biomaterials, 20 (1999) 1371-1380. 46. H. M. Fares, J. L. Zatz, J. Cosmet. Sci., 50 (1999) 133-146. 47. S. E. Dunn, A. Brindley, S. S. Davis, M. C. Davies, L. Illum, Pharm. Res., 11 (1994) 1016-1022. 48. Adalsteinsson, A. Lamotte, R. F. Baddour, C. K. Pollak, A. Colton., G. M. Whitesides, J. Molecular Catalysis, 6 (1979) 199. 49. S. Zalipsky, C. Gilon, A. Zilkha, Eur. Polym. J., 19 (1983) 1177-1183. 50. V. Carelli, G. Di Colo, E. Nannipieri, M. F. Serafini, J. Controlled Release, 33 (1995) 153-162. 51. L. Mu and S. S. Feng, J. Controlled Release, 86 (2003) 33–48 52. J. M. Dintaman, J. A. Silverman, Pharm. Res., 16 (1999) 1550–1556. 53. R. J. Sokol, N. Butler-Simon, C. Conner, J. E. Heubi, F. R. Sinatra, F. J. Suchy, M. B. Heyman, J. Perrault, R.J. Rot-hbaum, J. Levy, S. T. Iannaccone, B. L. Shneider, T. K. Koch, M. R. Narkewicz, Gastroenterology, 104 (1993) 1727–1735. 54. L. Mu and S. S. Feng, Pharmaceutical Research, 20 ( 2003) 1864-1872. 55. L. Mu and S. S. Feng, J. Controlled Release, 80 (2002) 129–144. 56. S. S. Feng , G. F. Huang, J. Controlled Release, 71 (2001) 53–69. 57. S. S. Feng, L. Mu, B. H. Chen, D. Pack, Mater Sci Eng CBiomimetic Supramol Syst, 20 (2002) 85-92.
摘要: 
本研究利用具生物降解性高分子共聚乳酸-甘醇酸(poly(lactide-co-glycolide);PLGA)包覆新型抗精神疾病藥物奧氮平(olanzapine),並製備出達到14~30天長效型植入式的肌肉注射劑型微粒。研究中PLGA分別利用水溶性高分子聚乙二醇(mPEG)及蔗糖(sucrose)進行化學改質,賦予PLGA具有雙性性質,進而改善由PLGA所製備之藥物微粒的非連續性釋放藥物行為。PLGA的化學改質透過N-hydroxysuccinimide (NHS)以DCC作為coupling agent使PLGA末端的羧酸官能基與mPEG或蔗糖形成共價鍵結,其化學改質率約70~85%,產率為80%。成功利用一次乳化法製備出表面光滑且結構紮實之PLGA/olanzapine微粒,粒徑約30 μm、藥物包覆效率約為72%。結果顯示,30 wt% PLGA (50/50, Mw 10000)與70 wt% PLGA (85/15, Mw 73000)摻混所製備之PLGA/olanzapine微粒,體外釋放以每日3~4 %速率持續釋放olanzapine長達一個月。

In this study, to develop intramuscularly injectable microparticles from biodegradable poly(lactide-co-glycolide) (PLGA) and chemically modified PLGA-PEG and PLGA-sucrose for long-term sustained release of olanzapine. PLGA was respectively conjugated with PEG and sucrose in order to enhance the amphiphilic property of the copolymer and, therefore, improve the discontinuous drug release profile that was usually observed from PLGA matrices. The conjugation of mPEG and sucrose with PLGA was achieved in this project via the activation of the end carboxyl group of PLGA with N-hydroxysuccinimide using DCC as the coupling agent, followed by aminolysis with mPEG-NH2 and trans-esterification with sucrose. The PLGA/olanzapine microparticles prepared by employing the oil-in-water emulsion/solvent evaporation technique have shown an average size of ca. 30 μm, an encapsulation efficiency of ca. 72%, and smooth particle surface and compact interior sturacture. The PLGA/olanzapine microspheres consisting of 30 wt% PLGA (50/50) and 70 wt% PLGA (85/15), exhibit a long-term sustained release behavior of olanzapine for up to 1 month in vitro.
URI: http://hdl.handle.net/11455/3151
其他識別: U0005-2308201314052900
Appears in Collections:化學工程學系所

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