Title

雙乳化法製備生物可分解聚酯奈米微粒之藥物釋放研究

Translated Titles

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

DOI

10.6846/TKU.2007.00981

Authors

蘇尹翎

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)

PublicationName

淡江大學化學工程與材料工程學系碩士班學位論文

Volume or Term/Year and Month of Publication

2007年

Academic Degree Category

碩士

Advisor

董崇民

Content Language

繁體中文

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
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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。