Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA.
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA; Laboratory of Chemical Design of Bionanomaterials, Faculty of Chemistry, M. V. Lomonosov Moscow State University, Moscow 119992, Russia.
Adv Drug Deliv Rev. 2020;156:80-118. doi: 10.1016/j.addr.2020.09.009. Epub 2020 Sep 24.
Over the last three decades, polymeric micelles have emerged as a highly promising drug delivery platform for therapeutic compounds. Particularly, poorly soluble small molecules with high potency and significant toxicity were encapsulated in polymeric micelles. Polymeric micelles have shown improved pharmacokinetic profiles in preclinical animal models and enhanced efficacy with a superior safety profile for therapeutic drugs. Several polymeric micelle formulations have reached the clinical stage and are either in clinical trials or are approved for human use. This furthers interest in this field and underscores the need for additional learning of how to best design and apply these micellar carriers to improve the clinical outcomes of many drugs. In this review, we provide detailed information on polymeric micelles for the solubilization of poorly soluble small molecules in topics such as the design of block copolymers, experimental and theoretical analysis of drug encapsulation in polymeric micelles, pharmacokinetics of drugs in polymeric micelles, regulatory approval pathways of nanomedicines, and current outcomes from micelle formulations in clinical trials. We aim to describe the latest information on advanced analytical approaches for elucidating molecular interactions within the core of polymeric micelles for effective solubilization as well as for analyzing nanomedicine's pharmacokinetic profiles. Taking into account the considerations described within, academic and industrial researchers can continue to elucidate novel interactions in polymeric micelles and capitalize on their potential as drug delivery vehicles to help improve therapeutic outcomes in systemic delivery.
在过去的三十年中，聚合物胶束已成为治疗化合物的极具前途的药物输送平台。特别是，将高功效和高毒性的难溶性小分子封装在聚合物胶束中。聚合物胶束在临床前动物模型中表现出改善的药代动力学特征，并提高了治疗药物的疗效和卓越的安全性。几种聚合物胶束制剂已进入临床阶段，正在临床试验中或已获准用于人体。这进一步激发了人们对该领域的兴趣，并强调需要进一步学习如何最好地设计和应用这些胶束载体，以改善许多药物的临床效果。在这篇综述中，我们提供了有关聚合物胶束用于增溶难溶性小分子的详细信息，主题包括嵌段共聚物的设计、药物在聚合物胶束中的包封的实验和理论分析、药物在聚合物胶束中的药代动力学、纳米药物的监管批准途径以及临床试验中胶束制剂的当前结果。我们旨在描述最新的信息，包括用于阐明聚合物胶束核心内分子相互作用的先进分析方法，以实现有效增溶以及分析纳米药物的药代动力学特征。考虑到所述的考虑因素，学术和工业研究人员可以继续阐明聚合物胶束中的新相互作用，并利用它们作为药物输送载体的潜力，以帮助改善全身给药的治疗效果。
