Dept. of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Biomaterials. 2012 Mar;33(9):2746-53. doi: 10.1016/j.biomaterials.2011.12.016. Epub 2012 Jan 9.
Nanocarriers can fulfill essential functions in the stabilization and delivery of drugs: they prevent solubility issues and degradation, reduce side effects and modify the pharmacokinetic profile. However, particle based pharmaceuticals are complex and thus challenging to scale up. As formulation routines account for a large fraction of production costs, reducing complexity in the process of assembly, loading and functionalization of nanoparticles is desirable. Unlike existing approaches with similar goals, our protocol is designed to minimize usage of material and time. Prerequisite to this elegant one-step-procedure is the controlled phase-separation of a hydrophobic peptide to nanoparticles, inducing concurrent cargo-entrapment and association of a protein corona. We demonstrate the process by assembling Flutax-2 containing peptide nanoparticles functionalized with transferrin. Cellular uptake of the particles and cargo release depend on specific particle-cell interactions via transferrin receptor. These data indicate corona-mediated delivery of membrane impermeable cargo in vitro by a particulate delivery system entirely composed of amino acids.
它们可以防止药物溶解度问题和降解，减少副作用，并改变药物的药代动力学特性。然而，基于颗粒的药物是复杂的，因此难以放大规模。由于制剂方案占生产成本的很大一部分，因此希望在纳米颗粒的组装、装载和功能化过程中降低复杂性。与具有类似目标的现有方法不同，我们的方案旨在最大限度地减少材料和时间的使用。这种优雅的一步法的前提是控制疏水性肽向纳米颗粒的相分离，诱导同时包裹货物和形成蛋白质冠。我们通过组装含有 Flutax-2 的肽纳米颗粒来证明这一过程，这些纳米颗粒用转铁蛋白进行了功能化。颗粒的细胞摄取和货物释放取决于通过转铁蛋白受体的特定颗粒-细胞相互作用。这些数据表明，通过完全由氨基酸组成的颗粒递药系统，体外通过膜不可渗透货物的蛋白质冠介导的递药。
