Norepinephrine奈米微粒製劑在經皮吸收之研究

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Title:	Norepinephrine奈米微粒製劑在經皮吸收之研究 Study on the Use of Norepinephrine Nanoparticle Preparation for Transdermal Absorption
Authors:	王俊傑 Chiun-Chieh Wang
Contributors:	林恆弘嘉南藥理科技大學：生物科技研究所
Keywords:	新腎上腺素奈米微粒親水凝膠 norepinephrine nanoparticles hydrogel transdermal absorption
Date:	2003
Issue Date:	2008-10-08 15:45:44 (UTC+8)
Abstract:	本研究主要為探討norepinephrine親水凝膠奈米微粒製劑之製備及其特性。含藥奈米微粒之製備是以親水凝膠包覆藥物，再使用均質研磨器製成奈米微粒；其物化性質是藉由粒徑分析、流變學和熱卡式分析來評估。於體外實驗中，則分別研究藥物之包埋率、藥物由奈米微粒之釋離、透皮試驗、皮膚內藥物殘存量以及長期安定性等，並以高效能液相層析儀進行分析與評估。結果顯示奈米微粒之粒徑大小分佈、包埋率、體外釋離以及體外透皮均受製備過程、藥物濃度、親水凝膠種類和使用之界面活性劑等因素的影響。其中，微粒粒徑大小分佈範圍是介於40nm到500nm之間；微粒懸液之流變學特性為擴張性(搖變稠)流體；為維持長期保存之安定性，微粒製劑需經冷凍乾燥後於低溫下保存，並可加水回復；其包埋率仍可高達81.32%。熱分析結果顯示，藥物與親水凝膠及賦型劑之間並無物理化學反應產生。體外釋離試驗中，微粒型藥物則呈現30-40% 之初期釋離，其持續釋離時間可長達24 小時以上。體外透皮試驗其結果顯示，微粒型藥物經皮輸移系統需添加界面活性劑來增加透皮速率及通透量，並減少透皮時間。而界面活性劑benzalkonium chloride及sodium lauryl sulfate之促進穿皮作用均較tween 80佳，其使用濃度以不高於1%為宜。 This study described the preparation and characterization of hydrogel nanoparticles containing the neurochemical messenger norepinephrine (NE). NE as a model drug was encapsulated in hydrogel nanospheres using homogenizer. The size of the NE-hydrogel nanoparticles was evaluated by using Zetasizer 3000HS particle size analyzer. The rheological properties of ointments including NE-hydrogel nanoparticles were characterized by Cone and Plate Viscometer. All drug-polymer interactions and the skins were assessed by Differential Scanning Calorimetry (DSC). For these nanoparticles, drug loading, in vitro release of drug from the nanoparticles, drug concentration after transdermal absorption , cumulative amount of drug in skin and long-term stability determination were quantified by high performance liquid chromatography (HPLC). The results revealed that particle size, encapsulation efficiency, in vitro release and transdermal absorption properties of the nanoparticles were affected by various hydrogels, preparative processes, surfactants and drug concentrations. The measured particle size distribution was ranged from 40nm to 500nm. The time-depentent behavior of ointments including NE-hydrogel nanoparticles was mentioned to as 〝Dilatant〞 flow and showed a shear-thickening liquid. In regard to the long-term stability, the results suggested that the product containing NE nanoparticles ought to be stored in the condition of lyophilized powder at lower temperature and recovered by adding double deionized water before used. The DSC determinations indicated that the physical and chemical interaction did not occur among the components during manufacturing process and reconstituted lyophilized powders. The encapsulation efficiency of NE in hydrogel nanoparticles was reached to 81. 32%. On the basis of in vitro release study, it revealed that NE was encapsulated in the hydrogel matrix, following the initial burst release of 30% to 40%, the release was sustained over the 24-hours study period. For　in vitro transdermal absorption study, the skins were treated as well as the ointments were added with and without different concentrations (0.5% and 1%) of various surfactants (benzalkonium chloride, sodium lauryl sulfate and tween 80), the experimental results revealed that the rapid permeability was correlated with surfactants and drug concentration, the skin barrier property was significantly compromised with benzalkonium chloride and　sodium lauryl sulfate treatment, tween 80 had a lesser effect on skin barrier property compared to benzalkonium chloride and　sodium lauryl sulfate (　1% > 0.5%, benzalkonium chloride > sodium lauryl sulfate > tween 80).
Relation:	校內外完全公開
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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