Perfluorodecalin-Filled Poly(n-butyl-cyanoacrylate) Nanocapsules as Potential Artificial Oxygen Carriers: Preclinical Safety and Biocompatibility.
Perfluorodecalin-Filled Poly(n-butyl-cyanoacrylate) Nanocapsules as Potential Artificial Oxygen Carriers: Preclinical Safety and Biocompatibility.
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全氟萘烷填充的聚（氰基丙烯酸正丁酯）纳米胶囊作为潜在的人工氧载体：临床前安全性和生物相容性。
DOI：
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发表时间：
2015
影响因子：
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通讯作者：
K. Ferenz
中科院分区：
文献类型：
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作者：
J. Laudien;C. Groß;C. Mayer;H. de Groot;M. Kirsch;K. Ferenz
关于人造血液替代品的开发，已经讨论了全氟十钙填充聚（正丁基氰基丙烯酸酯）纳米胶囊作为人工氧载体的用途。本研究的目的是深入研究界面聚合法制备的全氟十calin填充聚氰丙烯酸正丁酯纳米胶囊的临床前安全性和生物相容性。对纳米胶囊的物理和微生物稳定性进行了评估。麻醉大鼠静脉输注后，利用19F-NMR波谱和体内显微镜观察对全身参数、微循环、体内循环半衰期、酸碱/代谢状态、器官损伤和生物分布的影响。全氟十calin填充的聚氰丙烯酸正丁酯纳米胶囊在4周内表现出物理和微生物稳定性，体内循环半衰期为t1/2 = 30分钟。总的来说，所有的动物都能耐受静脉输注制备的纳米胶囊，即使发生了一些副作用。注射纳米胶囊后，小鼠平均动脉血压瞬间降低，肝脏微循环受损，肝、脾、小肠脏器/组织损伤，血浆乳酸脱氢酶、肌酸激酶、天冬氨酸转氨酶等酶活性升高。分布模式评估显示纳米胶囊在脾脏、肾脏和小肠中蓄积。全氟十钙填充的聚氰丙烯酸正丁酯纳米胶囊符合临床前药物开发的基本要求，但要使其成为新型的人工氧载体，还需要进一步的改进。
With regard to the development of artificial blood substitutes, perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules are already discussed for the use as artificial oxygen carriers. The aim of the present study was to thoroughly investigate the preclinical safety and biocompatibility of the perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules prepared by interfacial polymerization. Nanocapsules were assessed for physical and microbial stability. Subsequent to intravenous infusion to anesthetized rats, effects on systemic parameters, microcirculation, circulatory in vivo half-life, acid base/metabolic status, organ damage and biodistribution were evaluated using inter alia 19F-NMR spectroscopy and in vivo microscopy. Perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules displayed physical and microbial stability over a period of 4 weeks and the circulatory in vivo half-life was t1/2 = 30 min. In general, all animals tolerated intravenous infusion of the prepared nanocapsules, even though several side-effects occurred. As a consequence of nanocapsule infusion, a transient decrease in mean arterial blood pressure, impairment of hepatic microcirculation, organ/tissue damage of liver, spleen and small intestine, as well as an elevation of plasma enzyme activities such as lactate dehydrogenase, creatine kinase and aspartate aminotransferase could be observed. The assessment of the distribution pattern revealed nanocapsule accumulation in spleen, kidney and small intestine. Perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules conformed to basic requirements of drugs under preclinical development but further improvement is needed to establish these nanocapsules as novel artificial oxygen carriers.