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含有聚血红蛋白-酪氨酸酶纳米生物技术复合物的聚乙二醇-聚乳酸纳米胶囊用于黑色素瘤中酪氨酸的消耗:制备与表征

PEG-PLA Nanocapsules Containing a Nanobiotechnological Complex of Polyhemoglobin-Tyrosinase for the Depletion of Tyrosine in Melanoma: Preparation and Characterisation.

作者信息

Fustier Caroline, Chang Thomas M S

机构信息

Artificial Cells and Organs Research Center, Departments of Physiology, Medicine and Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

J Nanomedine Biotherapeutic Discov. 2012 Mar;2(1):1-9. doi: 10.4172/2155-983X.1000103.

Abstract

Poly (ethylene glycol)-poly (lactic acid) block-copolymer (PEG-PLA) was optimized and characterized using H-NMR spectrum and DSC thermogram. This was then used for the preparation of PEG-PLA nanocapsules containing polyhemoglobin-tyrosinase. Transmission electron microscopic and scanning electron microscopic studies showed round and non-aggregated nanocapsules with a PEG halo around each nanocapsule. Dynamic Light Scattering showed that the Z-average diameter was 65.2 ± 0.5 nm (mean ± SEM) and the polydispersity index was 0.262 ± 0.002. Factors controlling the diameters included the stirring speed of the reaction mixture and the size of the PLA block in the PEG-PLA copolymer. At the body temperature of 37oC, free tyrosinase lost all its enzyme activity after 8 hours. However, Polyhemoglobin-tyrosinase nanocapcules retained 80% of its initial activity after 8 hours. This paper contains the first part of our work on the preparation and characterisation of PEG-PLA Polyhemoglobin-tyrosinase nanocapsules. Preliminary result in rats shows that 1 intravenous injection lowers the systemic tyrosine level to 10-13% after 5 minutes. The result of the detailed study and the preliminary animal study in have led to our ongoing detailed animal research to be reported in subsequent papers.

摘要

聚(乙二醇)-聚(乳酸)嵌段共聚物(PEG-PLA)通过氢核磁共振谱和差示扫描量热法进行了优化和表征。然后将其用于制备含有多聚血红蛋白-酪氨酸酶的PEG-PLA纳米胶囊。透射电子显微镜和扫描电子显微镜研究显示,纳米胶囊呈圆形且不聚集,每个纳米胶囊周围有一个PEG晕圈。动态光散射表明,Z平均直径为65.2±0.5nm(平均值±标准误),多分散指数为0.262±0.002。控制直径的因素包括反应混合物的搅拌速度和PEG-PLA共聚物中PLA嵌段的大小。在37℃的体温下,游离酪氨酸酶在8小时后失去了所有酶活性。然而,多聚血红蛋白-酪氨酸酶纳米胶囊在8小时后仍保留其初始活性的80%。本文包含了我们关于PEG-PLA多聚血红蛋白-酪氨酸酶纳米胶囊制备和表征工作的第一部分。在大鼠身上的初步结果表明,一次静脉注射在5分钟后可将全身酪氨酸水平降低至10-13%。详细研究结果和初步动物研究结果促使我们进行正在进行的详细动物研究,并将在后续论文中报告。

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