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研究生:范國烜
研究生(外文):Guo-Xuan Fan
論文名稱:幾丁聚醣奈米粒之製備及其應用於紅黴素控制釋放之探討
論文名稱(外文):Preparation of Chitosan Nanoparticles and Their Application on the Controlled Release of Erythromycin
指導教授:張克亮
指導教授(外文):Ke-Liang Zhang
學位類別:碩士
校院名稱:國立海洋大學
系所名稱:食品科學系
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:81
中文關鍵詞:幾丁聚醣奈米控制釋放
外文關鍵詞:chitosannanoparticlescontrolled release
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摘要
奈米藥物輸遞系統可藉由改變藥物在人體內的分佈,達到高度靶向、控制藥物釋放、提高難溶藥物的溶解率及吸收率,增加藥效及減少藥物毒性等目的。本研究以三聚磷酸鈉(sodium tripolyphosphate)與幾丁聚醣作用形成的奈米微粒,比較不同分子量的幾丁聚醣所製成奈米粒之特性的差異,並觀察其對紅黴素包覆率及體外釋放速率的影響。
在幾丁聚醣奈米粒的特性分析方面,結果顯示當幾丁聚醣溶液濃度減少和三聚磷酸鹽溶液濃度減少時,粒徑有變小的趨勢;粒子散射強度平均粒徑分佈約在100~300 nm之間,而粒子數目平均粒徑分佈較廣,在60~300 nm之間。
將不同分子量之幾丁聚醣所製備出的奈米粒做比較,發現分子量較大的幾丁聚醣所製備出的奈米粒之粒徑(668 nm),要比低分子量的幾丁聚醣奈米粒粒徑大(283 nm和286 nm);用不同分子量的幾丁聚醣奈米粒包覆紅黴素其包覆率是以大分子量的幾丁聚醣包覆率較高,但平均包覆率不高,約在3.3%∼12.4%之間。
而在以紅黴素為模式藥所做的體外藥物釋放實驗方面,在pH 7.4環境下,20 kDa幾丁聚醣微粒在釋放第1個小時,其釋放量就超過50%,24小時後釋放量達94%;70 kDa的幾丁聚醣微粒在第4個小時釋放量才超過50%,大分子量的幾丁聚醣微粒(200 kDa) 24小時候,其釋放量還不到50%。進一步分析其釋放模式,200 kDa、70 kDa的幾丁聚醣微粒,其紅黴素釋放模式較趨近於間質化溶出模式(matrix-release model),20 kDa則偏向一級模式,所有的幾丁聚醣微粒之釋放模式都和零級模式有較大的差異。
Abstract
Nanoscale drug delivery system has been developed to convey a sufficient dose of drug to lesion, provide drug targeting, increase the efficiency of drug delivery and improve release profiles. The objectives of this study was to investigate the effect of chitosan molecular weight on chitosan nanoparticles characteristics prepared by ionotropic gelation and its application on the controlled release of erythromycin.
As the concentration of chitosan solution and TPP decreased, the mean particle size of chitosan nanoparticles decreased. The intensity averaged diameter was about 100~300 nm, and the number averaged diameter was about 60~300 nm.
The particle size (668 nm) of nanopaticles prepared with high Mw (200 kDa) was larger than that (283 nm and 286 nm) of nanoparticles made of low Mw chitosan (70 kDa and 20 kDa). When the Mw of chitosan increased, the loading efficiency of erythromycin increased.
Chitosan nanoparticles loaded with erythromycin were resuspended in pH 7.4 buffer solution for drug release study. The nanoparticles prepared from 20 kDa chitosan released 50% in 1 hour and reached 94% in 24 hours. The nanoparticles made of chitosan with an Mw of 70 kDa released 50% in 4 hours, whereas the nanoparticles made from chitosan with 200 kDa Mw did not release 50% until 24 hours. The release profiles of high Mw chitosan nanoparticles (200 kDa and 70 kDa) can be fitted to the matrix-release model. In contrast, the release profile of nanoparticles prepared from chitosan with an Mw of 20 kDa was close to the first-order release model.
目錄
摘要 Ⅰ
Abstract Ⅲ
目錄 Ⅳ
圖表目錄 Ⅵ
第壹章、前言 1
第貳章、文獻整理 3
一、奈米科技在藥物輸遞系統上的應用 3
二、幾丁質與幾丁聚醣 9
三、以幾丁聚醣製備奈米藥物載體 13
四、紅黴素 16
五、實驗構想 17
第參章、實驗材料與方法 19
3.1實驗藥品與儀器 19
3.2實驗步驟 20
3.3粒徑分析儀原理 27
第肆章、結果與討論 28
4.1製備幾丁聚醣奈米級微粒 28
4.2以紅黴素為模式藥之幾丁聚醣奈米微粒 31
第伍章、結論 36
參考文獻 37
圖表目錄
圖一 藥物的釋放速率、有效濃度和時間之關係 45
圖二 幾丁質、幾丁聚醣和纖維素的結構圖 46
圖三 紅黴素(Erythromycin)的結構式 47
圖四 幾丁聚醣奈米粒製備及其特性探討之實驗流程圖 48
圖五 幾丁聚醣溶液濃度和三聚磷酸鹽溶液濃度對幾丁聚醣奈米粒粒徑之影響 49
圖六 幾丁聚醣(70 kDa)奈米粒在穿透式電子顯微鏡下的觀察 50
圖七 幾丁聚醣(20 kDa)奈米粒在穿透式電子顯微鏡下的觀察 51
圖八 幾丁聚醣(200 kDa)奈米粒在穿透式電子顯微鏡下的觀察 52
圖九 掃瞄式電子顯微鏡圖片:(a) 幾丁聚醣微粒(200 kDa) (b)包覆有紅黴素之幾丁聚醣微粒(200 kDa) 53
圖十 掃瞄式電子顯微鏡圖片:(a) 幾丁聚醣微粒(70 kDa) (b) 包覆有紅黴素之幾丁聚醣粒(70 kDa) 54
圖十一 掃瞄式電子顯微鏡的圖片:(a) 幾丁聚醣微粒(20 kDa) (b) 包覆有紅黴素之幾丁聚醣微粒(20 kDa) 55
圖十二 不同分子量的幾丁聚醣奈米粒粒徑比較 56
圖十三 不同分子量的幾丁聚醣奈米粒之紅黴素包覆率 57
圖十四 紅黴素在不同酸鹼值溶液中濃度變化情形 58
圖十五 紅黴素標準品在37℃、pH 7.4環境下之檢量線 59
圖十六 紅黴素在pH 1.4溶液中降解的一級反應模式 60
圖十七 不同分子量的包藥幾丁聚醣奈米粒在pH 7.4環境下的溶離曲線 61
圖十八 不同分子量的包藥幾丁聚醣奈米粒在pH 1.4環境下的溶離曲線 62
圖十九 分子量200 kDa的幾丁聚醣奈米粒在pH 7.4環境下之溶離曲線 63
圖二十 分子量70 kDa的幾丁聚醣微粒在pH 7.4環境下之溶離曲線 64
圖二十一 分子量20 kDa的幾丁聚醣微粒在pH 7.4環境下之溶離曲線 65
表一 現代藥物輸遞技術的主要用途 66
表二 幾丁質和幾丁聚醣在醫學方面的應用 67
表三 原料幾丁聚醣的特性 68
表四 以不同濃度幾丁聚醣溶液和三聚磷酸鹽溶液製備奈米粒之中心組合實驗設計條件 69
表五 以不同濃度幾丁聚醣溶液和三聚磷酸鹽溶液製備奈米粒之粒徑 70
表六 以不同濃度幾丁聚醣溶液和三聚磷酸鹽溶液製備奈米粒之粒徑的RSREG回歸分析結果 71
表七 以不同濃度幾丁聚醣溶液和三聚磷酸鹽溶液製備奈米粒之特性 72
參考文獻
王偉、秦汶、李素清、薄淑琴,1991,甲殼素的分子量,應用化學,8(6):85-87。
蔡敏郎,1993。不同分子量、不同去乙醯程度的幾丁聚醣溶液的流變性質與膠囊物性的關係。國立台灣海洋大學水產科學研究所碩士論文。
劉正雄 譯(Shargel, L. and Yu, A. B. C. 1993. Applied Biopharmaceutics and Pharmacokinetics 3e),1994。應用生物藥劑學與藥物動力學。合記圖書出版社翻譯出版。台灣台北。
陳榮輝和金曉珍,1995,水產甲殼類廢棄物開發高經濟價值之幾丁質、幾丁聚醣、幾丁寡醣研究之規劃報導。科學發展月刊,23(6);550-562。
許昌泰,1996。紅黴素對胃腸動力的作用。當代醫學。23(5): 88-90。
曾厚,1997。Chtin與Chtosan之應用與現況發展。生物產業。8(2):102-108。
陳慶源,2000。幾丁聚醣在藥物運送系統上之應用。食品工業。32(4): 18-28。
廖俊凱和周慈怡 編譯,2001。藥物化學。合記圖書出版社。pp.390-394。
李昂,2001。奈米級顆粒在藥物輸遞的應用。化工資訊。10: 44-55。
胡淑芬,2001。奈米科技發展之介紹。毫微米通訊。8(4): 1-10。
蔣浩恩,2001。抗發炎高分子前驅藥之酵素催化水解及動力學之探討。高雄醫學大學藥學研究所碩士論文。
Aiba, S., Izumi, M., Minoura, N. and Fujiwara, Y. 1985. Studies on chitin. 2. Preparation and properties of chitin membranes. Carbohydr. Polym. 5: 285-289.
Allemann, E., Leroux, J. C., Gurnay, R. and Doelker, E. 1993. In vitro extended-release properties of drug-loaded poly( D, L lactide acid) nanoparticles produced by a salting-out procedure. Pharm. Res. 10: 1732-1737.
Anderson, L. C., Wise, D. L. and Howes, J. F. 1976. An injectable sustained release fertility control system. Contraception 13: 375-384.
Austin, P. R., Brine, C. J., Castle, J. E. and Zikakis, J. P. 1981. Chitin: New facets of research. Science. 212 ( 5 ) : 749-753.
Aynie, I. C., Vauthier, C., Fattal, E., Foulquire, M. and Couvreur, P. 1998. Alginate nanoparticles as a novel carrier for antisense oligonucleotide. In: J. E. Diederichs, R. Muler (Eds). Future Strategies of Drug Delivery with Particulate Systems. Medpharm Scientific Publisher. Stuttgart. pp. 5-10.
Banerjee, T., Mitra, S., Singh, A. K., Sharma, R. K. and Maitra, A. 2002. Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int. J. Pharm. 243: 93-105.
Barratt, G. M. 2000. Therapeutic applications of colloidal drug carriers. Pharm. Sci. & Technol. Today 3(5): 163-171.
Baxter, A., Dillon, M., Taylor, K. D. A. and Roberts, G. A. F. 1992. Improved method for i. r. determination of the degree of N-acetylation of chitosan. Int. J. Biol. Macromol. 14 ( 6 ) : 166-169.
Birnbaum, T. D., Kosmala, J. D., Henthorn, D. B. and Peppas, L. B. 2000. Controlled release of β-estradiol from PLAGA microparticles: The effect of organic phase solvent on encapsulation and release. J. Control. Rel. 65: 375-387.
Bodmeier, R. and McGinity, J. W. 1988. Solvent selection in the preparation of poly(D,L-lactide) microsphere prepared by the solvent evaporation method. Int. J. Pharm. 43: 179-186.
Brasseur, F., Couvreur, P., Kante, B., Deckers-passau, L., Roland, M., Deckers, C. and Speiser, P. 1980. Actinomycin D adsorbed on polymethylcyanoacrylate nanoparticles: increased efficiency against an experimental tumor. Eur. J. Cancer 16:1441-1445.
Calvo, P., Vila-Jato, J. L. and Alonso, M. J. 1996. Comparative in vitro evaluation of several colloidal systems, nanoparticles, nanocapsules and nanoemulsions as ocular drug carriers. J. Pharm. Sci. 85: 530-536
Calvo, P., Remunan-Lopez, J. L., Vila-Jato, J. L. and Alonso, M. J. 1997. Novel hydrophilic chitosan and chitosan/polyethylene oxide nanoparticles as protein carrier. J. Appl. Polym. Sci. 63: 125-132.
Chang, K. L. B., Tai, M. C. and Cheng, F. H. 2001. Kinetics and products of the degradation of chitosan by hydrogen peroxide. J. Agric. Food Chem. 49: 4845-4851.
Couvreur, P., Kante, B., Roland, M., Goit, P., Bauduin, P. and Speiser, P. 1979. Polycyanoacrylate nanocapsules as potential lysosomotropic carrier: preparation, morphology and sorptive properties. J. Pharm. Pharmcol. 31: 331-332.
Couvreur, P., Kante, B., Grislain, L., Roland, M. and Speiser, P. 1982. Toxicity of polyalkylcyanoacrylate nanoparticlesⅡ: Doxorubicin-loaded nanoparticles. J. Pharm. Sci. 71(7):790-792.
Couvreur, P., Dubernet, C. and Puisieux, F. 1995. Controlled drug delivery with nanoparticles: Current possibilities and future trends. Eur. J. Pharm. 41: 2-13.
Diepold, R., Kreuter, J., Guggenbul, P. and Robinson, J. R. 1989. Distribution of poly-hexyl-2-cyano-(3-14C)acrylate nanoparticles in healthy and chronically inflamed rabbit eyes. Int. J. Pharm. 54: 149-153.
Farrugia, C. A. and Grover, M. J. 1999. Gelatin behavior in dilute aqueous solutions: Designing a nanoparticulate formulation. J. Pharm. Pharmacol. 51: 643-649.
Felt, O., Buri, P. and Gurny, R. 1998. Chitosan: a unique polysaccharide for drug delivery. Drug Devel. Ind. Pharm. 11: 979-993.
Fernandez-Urrusuno, R., Calvo, P., Remunan-Lopez, J. L., Villa-Jato, J. L. and Alonso, M. J. 1999. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm. Res. 16: 1576-1581.
Fontana, G., Licciardi, M., Mansueto, S., Schillaci, D. and Giammona, G. 2001. Amoxicillin-loaded polyethylcyanocrylate nanoparticles: influence of PEG coating on the particle size, drug release rate and phagocytic uptake. Biomaterials 22: 2857-2865.
Grant, S., Blair, H. S. and Mckay, G. 1988. Water soluble derivatives of chitosan. Polym. Comm. 29: 342-344.
Gref, R., Minamitake, Y., Peracchia, M.T., Trubetskoy, V., Torchilin, V. and Langer, R. 1994. Biodegradable long-circulating polymeric nanospheres. Science 263: 1600-1603.
Higuchi, T. 1963. Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drug dispersed in solid matrices. J. Pharm. Sci. 52: 1145.
Jackanicz, T. M., Nash, H. A., Wise, D. L. and Gregory, J. B. 1973. Polylactic acid as a biodegradable carrier for contraceptive steroids. Contraception 8: 227-234.
Jung, T., Breitenbach, A. and Kissel, T. 2000. Sulfobutylated poly(vinyl alcohol) -graft-poly(lactide-co-glyclide) facilitate the preparation of small negative charged biodegradable nanospheres for protein delivery. J. Control. Rel. 67: 157-169.
Kawahima, Y., Yamamoto, H., Takeeuchi, H. and Kuno, Y. 2000. Mucoadhesive D, L-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm. Dev. Technol. 5: 77-85.
Knorr, D. 1984. Use of chitinous polymers in food: a challenge for food research ad development. Food Technol. 38 ( 1 ): 85~97.
Kriwet, B., Walter, E. and Kissel, T. 1998. Synthesis of bioadhensive poly(acrylic acid) nano-and microparticles using an inverse emulsion polymerization method for the entrapment of hydrophilic drug candidates. J. Control. Rel. 11: 269-278.
Lang, E. R., Kienzle-Sterzer, C. A., Rodriiquez-Sanchez, D. and Rha, C. K. 1982. Rheological behavior of a typical random coil polyelectrolyte: Chitosan. In: Chitin and Chitosan. Eds. Hirano, S. and Tokura, S. The Japanese Society of Chitin and Chitosan. pp. 34-38.
Lescure, F., Seguin, C., Breon, P., Bourrient, P., Roy, D. and Couvreur, P. 1994. Preparation and characterization of novel polymethylidene malonate(2.1.2.)-made nanoparticles. Pharm. Res. 16: 1576-1581.
Ma, Z. S., Yeoh, H. H. and Lim, L. Y. 2002. Formulation pH modulate the interaction of insulin with chitosan nanoparticles. J. Pharm. Sci. 91(6): 1396-1404.
Miyazaki, S., Ishii, K. and Nadai, T. 1981. The use of chitin and chitosan as drug carriers. Chem. Pharm. Bull. 29(10):3067-3072.
Muzzarelli, R. A. A. 1977. Chitin. Pergramon Press, Oxford. UK.
Muzzarelli, R. A. A. and Rocchett, R. 1985. Dependence of the degree of acetylation of chitosans by first derivative ultraviolet spectrophotometry. Carbohydr. Polym. 5: 461-472.
Nishioka, Y. and Yoshino, H. 2001. Lymphatic targeting with nanoparticle system. Adv. Drug Delivery Rev. 44: 55-64.
Niwa, T., Takeuchi, H., Hino, T., Kunou, N. and Kawashima, Y. 1993. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L- lactide/ glycolide copolymer by a novel spontaneous emulsification solvent diffusion method and the drug release behavior. J. Control. Rel. 25: 89-98.
Pan, Y., Li, Y. J., Zhao, H. Y., Zheng, J. M., Xu, H., Wei, G., Hao, J. S. and Cui, F. D. 2002. Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int. J. Pharm. 249: 139-147.
Paesen, J., Khan, K., Roets, E. and Hoogmartens, J. 1994. Study of the stability of erythromycin in neutral and alkaline solution by liquid chromatography on poly(styrene-divinylbenzene). Int. J. Pharm. 113: 215-222
Pitt, C. G., Gratzi, M. M., Jeffcot, A. R., Zweidinger, R. and Schindler, A. 1979. Sustained release drug delivery systems Ⅱ: factors affects release rate for poly(ε-caprolactone) and related biodegradable polyesters. J. Pharm. Sci. 68: 1534-1538.
Quintanar, G. D., Ganem, Q. A., Alleman, E., Fessi, H. and Doelker, E. 1998. Influence of stabilizer coating layer on the purification and freeze drying of poly(D, L- lactide acid) nanoparticles prepared by emulsification-diffusion technique. J. Microencap. 15: 107-119.
Ruiz-Herrera, J., Muzzarelli, R. A. A. and Pariser, E. R. 1978. In Proceeding of the First International Conference on Chitin/Chitosan. MIT Sea Grant Program. Cambridge. Mass. pp.11.
Roberts, G. A. F. 1992. Chitin Chemistry. pp: 65-83, The Macmillan Press LTD, London, pp: 1-53.
Roy, K., Mao, H. Q., Huang, S. K. and Leong K. W. 1999. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nature Med. 5(4): 387-391.
Sakr, F. M. 1999. A programmable drug delivery system for oral administration. Int. J. Pharm. 184: 131-139.
Sandford, P. A. 1989. Chitosan: Commercial uses and pontential applications. In: Chitin and Chitosan. Eds. Skjak-Braeek, G., Athonsen, T. and Sandford, P. Elsevier Applied Sci. Pulishers, New York. pp. 52-63.
Sershen, S., Westcott, S., Halas, H. J., and West, J. 2000. Temperature-sensitive polymer-nanoshell composite for photothermally modulated drug delivery. J. Biomed. Mat. Res. 51: 293-298.
Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R. and Rudzinski, W. E. 2001. Biodegradable polymeric nanoparticles as drug delivery device. J. Control. Rel. 70: 1-20.
Stanley, W. L., Watters, G. G., Chan, B. G. and Mercer, J. M. 1975. Lactose and other enzymes bound to chitin with glutaraldehyde. Biotech. Bioeng.ⅩⅧ: 315-326.
Stenekes, R. J. H., Loebis, A. E., Fernandes, C. M., Crommelin, D. J. A. and Hennick, W. E. 2000. Controlled release of liposomes from biodegradable dextran microspheres: A novel delivery concept. Pharm. Res. 17: 690-695.
Stithit, S., Chen, W. and Price, J. C. 1998. Development and characterization of buoyant theophylline microspheres with near zero order release kinetics. J. Microencap. 15: 725-737.
Vandorpe, J. and Schacht, E. 1997. Long circulating biodegradabale poly(phosphazene) nanoparticles surface modified with poly(phosphazene)-polyethyene oxide copolymer. Biomaterials 18: 1141-1152.
Wehrle, P., Magenhein, B. and Benita, S. 1995. The influence of process parmeters on the PLA nanoparticle size distribution evaluated by means of factorial design. J. Pharm. Biopharm. 41: 19-26.
Wise, D. L., Fellman, T. D., Sanderson, J. E. and Wentworth, R. L. 1979. Lactide/glycolide acid polymers in: G. Geregoriadis (Ed.). Drug Carriers in Biology and Medicine. Academic Press. London. 237-270.
Xu, Y. and Du, Y. 2003. Effect of molecular structure of chitosan: protein delivery properties of chitosan nanoparticles. Int. J. Pharm. 250: 215-226.
Zambaux, M. F., Bonneaux, F., Gref, R., Maincent, P., Dellacherie, E., Alonso, M. J., Labrude, P. and Vigneron, C. 1998. Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by double emulsion method. J. Control. Rel. 50: 31-40.
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1. 許昌泰,1996。紅黴素對胃腸動力的作用。當代醫學。23(5): 88-90。
2. 曾厚,1997。Chtin與Chtosan之應用與現況發展。生物產業。8(2):102-108。
3. 陳慶源,2000。幾丁聚醣在藥物運送系統上之應用。食品工業。32(4): 18-28。
4. 2. 江豐富(1995),「以文憑還是以人力資本取才-台灣地區實證研究」,教育研究資訊,第3卷,第5期,頁17-35。
5. 3. 徐聯恩、謝瑞史(1999),「創新性人力資源管理制度概況及其對企業績效之影響」,勞資關係,第17卷,第11期,頁40-52。
6. 4. 張火燦(1991),「組織內部勞動市場的形成及其雇用系統」,工業職業教育,第10卷,第2期,頁26-31。
7. 5. 張晉芬(1993),「企業組織中升遷機會的決定及員工的期望-兼論內部勞動市場理論的應用」,中央研究院人文及社會科學集刊,第6卷,第1期,頁205-230。
8. 7. 陳心田(2002),「學歷、經歷與網絡─軍人晉升至上校等待時間之分析」,人力資源管理學報,第2卷,第4期,頁33-56。
9. 10. 廖麗佳(1998),「人力資源策略與企業策略關係之探討」,就業與訓練,第17卷,第5期,頁62-66。
10. 11. 趙其文(1992),「從職務升遷論職務列等」,人事月刊,12月份,頁39-47。
11. 12. 趙其文(1999),「綜論現代人力資源管理」,人事月刊,7月份,頁43-57。
12. 13. 蔡敦浩、葉匡時、俞慧芸(1993),「從社會資本學說論我國產業政策之發展方向」,研考雙月刊,第17卷,第1期,頁44-56。
 
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