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標題: | Pluronic®嵌段共聚合物包覆脂質微粒作為節絲菌素B載體之研究 Lipid-nanoparticles Coated with Pluronic® Block Copolymer as a Carrier for Amphotericin B |
作者: | Yu-Ting Hung 洪妤婷 |
指導教授: | 高純琇 |
關鍵字: | 嵌段共聚合物,節絲菌素B,脂質,膠體藥物載體,難溶性藥物, Pluronic block copolymer,amphotericin B,lipid,colloidal drug delivery system,hydrophobic drug, |
出版年 : | 2008 |
學位: | 碩士 |
摘要: | 近年來,藥物載體的發展尤其是膠體藥物載體(colloidal drug delivery systems, CDDS)受到相當大的重視,脂質藥物載體是由生物體中本身具有的脂質所構成,具有毒性很低等優點,被認為是相當安全的一種藥物載體。然而,由單一脂相構成的脂質載體可能會有突釋效應及難以達到零級釋放等潛在問題,為了克服這些限制,曾有學者製備以含藥脂質為核、Pluronic嵌段共聚合物為殼的奈米粒。
本研究中,藉由加入Pluronic嵌段共聚合物於事先形成的卵磷脂脂質微粒中,使聚合物以物理性吸附方式塗佈於脂質微粒表面,並測量不同PEO/PPO比例之聚合物對於形成微粒之平均粒徑及表面電位的影響。研究結果顯示比較相同PPO嵌段的聚合物,含較長PEO鏈的聚合物比短PEO鏈的聚合物造成較多粒徑增加,而在PEO數相同的情況下,含較長PPO鏈的聚合物亦有較多粒徑增加。但本實驗中之脂質微粒系統的平均粒徑及分散性可能造成實驗結果判斷的誤差。表面電位的結果,則顯示加入聚合物濃度愈高,表面電位降低程度愈大,最終會到達一平原期。在PPO數相同的情況下,含較長PEO鏈的聚合物其降低表面電位的效果較大,另一方面,PEO數相同時,PPO段愈長的聚合物亦有較大的表面電位降低效果,表示PPO段亦可能影響切面自粒子表面位移。 在本研究的第二部分,將模式藥物節絲菌素B包覆至脂質微粒中,最終成品濃度1.19 mg/mL,包覆率為79.05%。從藥物釋放曲線可看出聚合物外殼可減緩藥物釋出,其中,PPO段對於藥物釋放的影響較大,顯示PPO嵌段與磷脂質之間或是PPO嵌段與amphotericin B之間的作用力為影響amphoteririn B釋放的主要因素,而PEO段對於藥物釋放的影響相較之下較PPO段不顯著。 Recent advances in nanoparticle systems in drug delivery display a great potential for the administration of active molecules. The lipid systems with physiological lipids have the advantages of low toxicity. However, lipid-based drug carriers composed of a single lipid phase have some inherent problems of burst effect and difficulty in a zero-order release. To overcome these limitations, researchers prepared nanoparticles with drug-loaded lipid as the core and Pluronic triblock copolymer as the shell. In this study, Pluronic block copolymers were physically adsorbed to the surface of lipid-nanoparticles by adding the copolymer molecules to preformed lecithin-based lipid-nanoparticle suspension. The effect on the mean vesicle diameter and zeta-potential was monitored for Pluronic block copolymers with different PEO/PPO ratios. It was found that the polymers composed of the same PPO but longer PEO chains can cause more increase in vesicle diameter than those composed of shorter PEO chains, and so did polymers composed of the same PEO but longer PPO chains. However, the bigger size and polydispersity of the vesicles may result in experimental errors in this study. The zeta-potential values obtained showed reduction in the zeta-potential with increase in block copolymer concentration and eventually a plateau was reached. The reduction in zeta-potential is bigger for polymers with higher PEO chains when PPO blocks are the same. On the other hand, polymers with more PPO resulted in bigger reduction in zeta-potential, indicating that the PPO blocks may also have some effects on the shift of the shear plane. In the second part of this study, the model drug amphotericin B was incorporated into the lipid-nanoparticles, with encapsulation efficiency of 79.05% and concentration of 1.19 mg/mL. The release profiles showed that the polymer shell can reduce the release rate of amphotericin B. The higher the polymer concentration, the slower the release of amphotericin B from vesicles. Besides, longer PPO chain length demonstrated obvious effects on drug release, indicating that there existed interactions between the PPO block and phospholipids or interactions between the PPO block and amphotericin B molecules. On the other hand, the PEO chain length has very little effect on the release of amphotericin B. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/27448 |
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顯示於系所單位: | 藥學系 |
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