Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich (ETH Zürich), Wolfgang-Pauli-Straße 10, 8093 Zurich, Switzerland.
ACS Nano. 2013 Sep 24;7(9):8243-50. doi: 10.1021/nn4037317. Epub 2013 Aug 27.
Many potent drugs are difficult to administer intravenously due to poor aqueous solubility. A common approach for addressing this issue is to process them into colloidal dispersions known as "nanocrystals" (NCs). However, NCs possess high-energy surfaces that must be stabilized with surfactants to prevent aggregation. An optimal surfactant should have high affinity for the nanocrystal's surface to stabilize it, but may also include a trigger mechanism that could offer the possibility of altering size distribution and uptake of the NC. This study presents a modular and systematic strategy for optimizing the affinity of polymeric stabilizers for drug nanocrystals both before and after oxidation (i.e., the selected trigger), thus allowing for the optimal responsiveness for a given application to be identified. A library of 10 redox-responsive polymer stabilizers was prepared by postpolymerization modification, using the thiol-yne reaction, of two parent block copolymers. The stabilizing potential of these polymers for paclitaxel NCs is presented as well as the influence of oxidation on size and dissolution following exposure to reactive oxygen species (ROS), which are strongly associated with chronic inflammation and cancer. Owing to the versatility of postpolymerization modification, this contribution provides general tools for preparing triggered-sheddable stabilizing coatings for nanoparticles.
许多强效药物由于水溶性差而难以静脉给药。解决这个问题的一种常见方法是将它们加工成胶体分散体，称为“纳米晶体”（NCs）。然而，NCs 具有高能表面，必须用表面活性剂稳定以防止聚集。理想的表面活性剂应该对纳米晶体的表面具有高亲和力以稳定它，但也可能包括一个触发机制，这可能提供改变 NC 的尺寸分布和摄取的可能性。本研究提出了一种模块化和系统的策略，用于优化聚合物稳定剂对药物纳米晶体的亲和力，包括氧化前后（即所选触发），从而可以确定给定应用的最佳响应性。通过使用硫醇-炔反应，对两种母体嵌段共聚物进行聚合后修饰，制备了 10 种氧化还原响应性聚合物稳定剂库。这些聚合物对紫杉醇 NCs 的稳定潜力以及氧化对 ROS（与慢性炎症和癌症密切相关）暴露后尺寸和溶解的影响也得到了研究。由于聚合后修饰的多功能性，本研究为制备用于纳米颗粒的触发式可脱落稳定涂层提供了通用工具。
