In Vivo Characterization of the Biodistribution Profile of Amphipol A8-35
In Vivo Characterization of the Biodistribution Profile of Amphipol A8-35
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DOI：
10.1007/s00232-014-9682-8
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发表时间：
2014-10-01
影响因子：
2.4
通讯作者：
Bagnard, D.
中科院分区：
文献类型：
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作者：
Fernandez, A.;Le Bon, C.;Bagnard, D.
Amphipols（APols）是聚合物表面活性剂，其在不存在去污剂的情况下保持膜蛋白（MP）的水溶性，同时使其稳定。它们可用于在体内递送MP和其他疏水分子以用于治疗目的，例如，疫苗接种或靶向药物递送。最佳表征的APol（称为A8-35的聚丙烯酸酯衍生物）的生物分布和消除已经在小鼠中使用两种荧光APol（移植有Alexa Fluor 647或罗丹明）进行了检查。使用了三种最常见的注射途径，静脉内（IV）、腹膜内（IP）和皮下（SC）。通过体内荧光成像和测定主要器官中荧光团的浓度研究了生物分布。游离罗丹明用作对照。静脉注射后，A8-35迅速分布在整个生物体中，并在大脑和脾脏以外的大多数器官中发现，然后缓慢消除（10-20天）。在IP注射后观察到类似的模式，随后是短暂的潜伏期，在此期间聚合物保持局限于腹膜腔。SC注射后，A8-35基本上保留在注射点，仅缓慢释放。一个有趣的观察结果是，A8-35倾向于在脂肪垫中积累，这表明它可以用于提供抗肥胖药物。
Amphipols (APols) are polymeric surfactants that keep membrane proteins (MPs) water-soluble in the absence of detergent, while stabilizing them. They can be used to deliver MPs and other hydrophobic molecules in vivo for therapeutic purposes, e.g., vaccination or targeted delivery of drugs. The biodistribution and elimination of the best characterized APol, a polyacrylate derivative called A8-35, have been examined in mice, using two fluorescent APols, grafted with either Alexa Fluor 647 or rhodamine. Three of the most common injection routes have been used, intravenous (IV), intraperitoneal (IP), and subcutaneous (SC). The biodistribution has been studied by in vivo fluorescence imaging and by determining the concentration of fluorophore in the main organs. Free rhodamine was used as a control. Upon IV injection, A8-35 distributes rapidly throughout the organism and is found in most organs but the brain and spleen, before being slowly eliminated (10-20 days). A similar pattern is observed after IP injection, following a brief latency period during which the polymer remains confined to the peritoneal cavity. Upon SC injection, A8-35 remains essentially confined to the point of injection, from which it is only slowly released. An interesting observation is that A8-35 tends to accumulate in fat pads, suggesting that it could be used to deliver anti-obesity drugs.