Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, United Kingdom; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
Biomaterials. 2018 Sep;178:570-582. doi: 10.1016/j.biomaterials.2018.03.047. Epub 2018 Mar 29.
Size and shape have progressively appeared as some of the key factors influencing the properties of nanosized drug delivery systems. In particular, elongated materials are thought to interact differently with cells and therefore may allow alterations of in vivo fate without changes in chemical composition. A challenge, however, remains the creation of stable self-assembled materials with anisotropic shape for delivery applications that still feature the ability to disassemble, avoiding organ accumulation and facilitating clearance from the system. In this context, we report on cyclic peptide-polymer conjugates that self-assemble into supramolecular nanotubes, as confirmed by SANS and SLS. Their behaviour ex and in vivo was studied: the nanostructures are non-toxic up to a concentration of 0.5 g L and cell uptake studies revealed that the pathway of entry was energy-dependent. Pharmacokinetic studies following intravenous injection of the peptide-polymer conjugates and a control polymer to rats showed that the larger size of the nanotubes formed by the conjugates reduced renal clearance and elongated systemic circulation. Importantly, the ability to slowly disassemble into small units allowed effective clearance of the conjugates and reduced organ accumulation, making these materials interesting candidates in the search for effective drug carriers.
尺寸和形状逐渐成为影响纳米药物输送系统性质的关键因素之一。特别是，人们认为细长的材料与细胞的相互作用不同，因此可能允许在不改变化学成分的情况下改变体内命运。然而，挑战仍然是为具有各向异性形状的输送应用创造稳定的自组装材料，这些材料仍然具有能够进行解组装的能力，从而避免器官积累并促进从系统中清除。在这种情况下，我们报告了环肽-聚合物缀合物，这些缀合物通过 SANS 和 SLS 确认为超分子纳米管自组装。研究了它们在 ex 和 in vivo 的行为：纳米结构在浓度高达 0.5 g/L 时是无毒的，细胞摄取研究表明，进入的途径是依赖能量的。肽-聚合物缀合物和对照聚合物静脉注射到大鼠后的药代动力学研究表明，缀合物形成的纳米管的较大尺寸降低了肾脏清除率并延长了系统循环。重要的是，缓慢解组装成小单元的能力允许有效清除缀合物并减少器官积累，使这些材料成为寻找有效药物载体的有前途的候选物。
