Translated Titles

Studies on drug release behavior of biodegradable poly(hydroxyalkanoate) nanoparticles prepared by a double emulsion method





Key Words

奈米微粒 ; 聚羥基丁酯-羥基己酯 ; 鹽酸四環素 ; 藥物釋放 ; nanoparticles ; hydrochloride tetracycline ; drug release ; poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)



Volume or Term/Year and Month of Publication


Academic Degree Category




Content Language


Chinese Abstract

本研究以生物可分解塑膠PHBHHx作為載體,利用雙乳化(Double emulsion, W1/O/W2)溶劑揮發法製造奈米微粒。首先利用NMR、FTIR對PHBHHx做結構鑑定,確認其HHx含量,並且測量分子量和熱性質。利用雙乳化溶劑揮發法製備微粒,內部水相(W1)、油相(O, CHCl3)及外部水相(W2)的體積比為1:5:30,同時於外部水相添加界面活性劑及不同含量之PVA增稠劑,利用超音波細胞破碎機進行乳化,溶劑揮發完畢後,乳液中微粒之粒徑在200-300nm之間,隨著PVA含量從0.2%增加至1%,粒徑從296nm減小至205nm。另外實驗也發現在相同條件下,利用HHx含量為10%之PHBHHx共聚物作為載體所得到之微粒粒徑稍微小於以HHx含量為5%之PHBHHx共聚物作為載體所得之微粒,這是由於PHBHHx10的分子量小於PHBHHx5,而造成油相黏度減小,若降低PHBHHx在油相中之濃度,則由於黏度之降低,也可減小微粒之粒徑。 最後選擇HHx含量為10%的PHBHHx作為載體去包覆鹽酸四環素或稱四環素鹽酸鹽(tetracycline hydrochloride),利用ATR-FTIR分析微粒,可以得知在微粒的表面上有藥物的殘留,而隨著藥物添加量的增加,殘留量越多。藉由TGA分析發現,PHBHHx的熱裂解溫度約在280oC,而包覆藥物的微粒熱裂解溫度提昇了20 oC。計算不同藥物包覆量微粒的產率(yield,%)、微粒內藥物的含量(loading,%)、包覆率(encapsulation efficiency,%),所得微粒產率在71-86%之間,承載率在3.5-2.2%之間,而包覆率則在26-54%之間,並且隨著藥物添加量的增加而降低。 將不同藥物含量的微粒置於透析袋中於去離子水中釋放,所有的微粒呈現出非常輕微的突釋現象。藥物釋放過程中,當微粒所含的藥物量越多釋放速率越快,且微粒的釋放屬於一階段模式的釋放行為,80%的藥物都於此階段釋放。

English Abstract

In this study, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)(PHBHHx) nanoparticles containing hydrochloride tetracycline, as a model of water-soluble drugs, were prepared by W1/O/W2 emulsion using a sonicator and a solvent evaporation method. Two PHBHHx copolymers, namely PHBHHx5 and PHBHHx10, were in this study, which had 5.0 and 9.1% HHx content in composition, respectively. GPC results rvealed that they also had different molecular weight, in which PHBHHx5 had a molecular weight (Mw) of 653000, and the other one PHBHHx10, 348000. In double emulsion (W1/O/W2), the ratio of internal aqueous phase (W1), oil phase (O) and external aqueous phase (W2) was 1:5:30 (v/v/v), in which the external aqueous containing surfactant (Tween80) and PVA used as a stabilizer. After emulsification and solvent evaporation, particle size distribution was measured using laser light scattering method, and found to be between 200 and 300nm.Particle size decreasesd from 296nm to 205nm with increasing the PVA content from 0.2%(w/v) to 1%(w/v). Under the same experimental conditions, particles prepared by PHBHHx5 those were smaller than prepared by PHBHHx10.This is because the molecular weight of PHBHHx10 is smaller than that of PHBHHx5 and thus, the viscosity in oil phase would be smaller.Furthermore, the viscosity in oil phase and the particle size decreased as the concentration of PHBHHx in oil phase decreased. PHBHHx10 was chosen as a carrier to encapsulate hydrochloride tetracycline. ATR-FTIR was utilized to investigate the residual drug on surfaces of nanoparticles. It indicated that the residual drug on surface increased as the added amount of drug were increased.TGA thermograms shows that the maximum degradation temperature of PHBHHx was about 280oC, and that of nanoparticles containing drug were raised up to about 300oC. After encapsulation yield, loading and encapsulation efficiency were all calculated. The results revealed that the yield were between 71-86%, loading 3.5-2.2% and encapsulation efficiency 26-54%, and the encapsulation efficiency decreased with the adding amount of drug. After 10 hours in deionized water, drug release amount of all nanoparticles reached 80%.

Topic Category 工學院 > 化學工程與材料工程學系碩士班
工程學 > 工程學總論
工程學 > 化學工業
  1. A.Belbella, C. Vauthier, H. Fessi, J.P. Devissaguet, F. Puisieux (1996) . In vitro degradation of nanospheres from poly(D,L- lactides) of different molecular weights and polydispersities. International Journal of Pharmaceutics, 129, 95–102.
  2. Avinash Budhian, Steven J. Siegel , Karen I. Winey (2007). Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content. International Journal of Pharmaceutics, 336, 367–375.
  3. C. S. K. Reddy, R. Ghai, Rashmi and V. C. Kalia. (2002). Polyhydroxyalkanoates: an overview. Bioresource Technology, 82(2), 137-146.
  4. Carlos H. Villa, Louise B. Lawson, Yimin Li, and Kyriakos D. Papadopoulos. (2003). Internal Coalescence as a Mechanism of Instability in Water-in-Oil-in-Water Double-Emulsion Globules. Langmuir, 19, 244-249.
  5. E.L. Culler (1997). Diffusion: Mass Transfer in Fluid Systems Second Edi-tion. America: Cambridge University Press, 467-478.
  6. Dilek Sendil, Ihsan Gu¨rsel, Donald L. Wise, Vasıf Hasırcı. (1999). Antibiotic release from biodegradable PHBV microparticles. Journal of Controlled Release, 59, 207-217.
  7. F. Boury, Tz. Ivanova, I. Pana¨ıotov, J.E. Proust, A. Bois andJ. Richou (1995). Dynamic properties of poly(D,L-lactide) andpolyvinyl alcohol monolayers at the air / water and dichloromethane/water interfaces, Journal Colloid Interface Science, 169, 380–392.
  8. T. Florence, J.A. Rogers (1971). Emulsion stabilization by non-ionic surfactants: experiment and theory, Journal of Pharmacy and Pharmacology , 23, 233-251.
  9. Iosif Daniel Rosca, Fumio Watari, Motohiro Uo. (2004). Microparticle formation and its mechanism in single and double emulsion solvent evaporation. Journal of Controlled Release, 99, 271-280.
  10. Jayanth Panyam , Manisha M. Dali , Sanjeeb K. Sahoo , Wenxue Ma ,Sudhir S. Chakravarthi , Gordon L. Amidon , Robert J. Levy ,Vinod Labhasetwar (2003). P olymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano- and microparticles. Journal Controlled Release, 92, 173–187.
  11. Jeonghee Surh, Eric A. Decker, D. Julian McClements (2005). Properties and stability of oil-in-water emulsions stabilized by fish gelatin. Food Hydrocolloids, 20, 596-606
  12. Kamala Rani Acharva, Subhash C. Bhattacharyya, Satya P. Moulik. (1999). Effects of carbohydrates on the solution properties of surfactants and dye-micelle complexation. Journal of Photochemistry and Photobiology A:Chemistry, 122, 47-52.
  13. M.A. Martin, F.C. Miguens, J. Rieumont, R. Sanchez. (2000). Tailoring of the external and internal morphology of poly-3-hydroxy butyrate microparticles. Colloids and Surfaces, 17, 111-116
  14. M.F. Zambaux, F. Bonneaux, R. Gref, P. Maincent, E. Dellacherie, M.J. Alonso, P. Labrude , C. Vigneron (1998). Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method.Journal of controlled release, 50, 31-40
  15. Michael Ku¨hne, Gerd Hamscher, Ute Ko¨rner, Dagmar Schedl, Siegfried Wenzel. (2001). Formation of anhydrotetracycline during a high-temperature treatment of animal-derived feed contaminated with tetracycline. Food Chemistry , 75, 423-429.
  16. Nissim Garti. (1997). Double emulsions -- scope, limitations and new achievements. Colloids and surfaces, 123-124, 233-246.
  17. P.D. Scholes, A.G.A. Coombes, L. Illum, S.S. Davis, M.Vert, M.C. Davies (1993). The preparation of sub-200 nm poly(lactide-co-glycolide) microspheres for site-specific drug delivery. Journal Controlled Release, 25, 145–153.
  18. Sanjeeb K. Sahoo, Jayanth Panyam, Swayam Prabha, Vinod Labhasetwar (2002). Residual polyvinyl alcohol associated with poly (D,L-lactide-coglycolide) nanoparticles affects their physical properties and cellular uptake. Journal of controlled release, 82, 105-114
  19. Schramm, L. Laurier (2005).Emulsions, Foams, and Suspensions: Fundamentals and Applications
  20. Seung Chan Lee, Jae Taek Oh, Myoung Ho Jang, Soo Il Chung (1999). Quantitative analysis of polyvinyl alcohol on the surface of poly(D,L-lactide-co-glycolide) microparticles prepared by solvent evaporation method: effect of particle size and PVA concentration. Journal Controlled Release, 59, 123–132.
  21. K. Sudesh, H. Abe, Y. Doi (2000). Synthesis, structure and properties of polyhydroxyalkanoates: Biological polyesters. Progress in Polymer Science, 25, 1503-1555.
  22. Fa´tima Varanda, Maria J. Pratas de Melo, Ana I. Cacüo, Ralf Dohrn, Foteini A. Makrydaki, Epaminondas Voutsas, Dimitrios Tassios, and Isabel M. Marrucho.(2006). Solubility of Antibiotics in Different Solvents. 1. Hydrochloride Forms of Tetracycline, Moxifloxacin, and Ciprofloxacin. Industrial & Engineering Chemistry, 45, 6368-6374.
  23. S. Yolles, J. E. Eldrige, J. H. R. Woodland (1970). Sustained delivery of drugs from polymer/drug mixtures. Polymer News, 1(4-15), 9-15.
  24. 王賢達、鍾瑞芬,(2002),聚酯微粒之水解和藥物釋放研究。國立台北科技大學高分子研究所碩士論文,
  25. 余秀瑛,(2001),微脂粒為藥物載體之研究。國科會生命科學簡訊,2, 15
  26. 李嘯風、陳志榮、李浩然、劉迪霞、韓世鈞,(2000),Span80-Tween-菜油-水乳化體系中最佳HLB值與乳化劑總用量的關係。國家自然科學基金重點資助課題
  27. 孫一明、許紹菁,(1999),微粒包覆技術及其在藥物制放上之應用。 化工技術,7, 5
  28. 陳建海,S. S. Davis, 陳志良,(2000),聚羥基丁酸酯-羥基戊酸酯共聚物/明膠微粒的構造型態與性能。高分子材料科學與工程, 16,5.
  29. 蔡燕鈴、陳暉,(2001),溶劑揮發法包覆水溶性藥物之研究。行政院國家科學委員會專題研究成果報告
  30. 蔡燕鈴、陳暉,(2002),生醫高分子於藥物傳輸之應用。化工技術,10, 3
Times Cited
  1. 吳書璇(2014)。製備多孔性聚乳酸微粒於軟組織填補劑之開發。臺北科技大學生物科技研究所學位論文。2014。1-57。 
  2. 黃曼婷(2013)。開發多孔性聚乳酸微粒作為軟組織填補劑之應用。臺北科技大學化學工程研究所學位論文。2013。1-95。