Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, United States.
Department of pharmacology, University of Michigan, Ann Arbor, MI 48019, United States.
J Colloid Interface Sci. 2018 May 15;518:174-183. doi: 10.1016/j.jcis.2018.02.030. Epub 2018 Feb 9.
Though the emulsion solvent evaporation (ESE) technique has been previously modified to produce rod-shaped particles, it cannot generate small-sized rods for drug delivery applications due to the inherent coupling and contradicting requirements for the formation versus stretching of droplets. The separation of the droplet formation from the stretching step should enable the creation of submicron droplets that are then stretched in the second stage by manipulation of the system viscosity along with the surface-active molecule and oil-phase solvent.
A two-step ESE protocol is evaluated where oil droplets are formed at low viscosity followed by a step increase in the aqueous phase viscosity to stretch droplets. Different surface-active molecules and oil phase solvents were evaluated to optimize the yield of biodegradable PLGA rods. Rods were assessed for drug loading via an imaging agent and vascular-targeted delivery application via blood flow adhesion assays.
The two-step ESE method generated PLGA rods with major and minor axis down to 3.2 µm and 700 nm, respectively. Chloroform and sodium metaphosphate was the optimal solvent and surface-active molecule, respectively, for submicron rod fabrication. Rods demonstrated faster release of Nile Red compared to spheres and successfully targeted an inflamed endothelium under shear flow in vitro and in vivo.
尽管乳液溶剂蒸发（ESE）技术已经过先前的修改以生产棒状颗粒，但由于液滴形成与拉伸之间固有的耦合和相互矛盾的要求，它不能产生用于药物输送应用的小尺寸棒。将液滴形成与拉伸步骤分开，应该能够产生亚微米级的液滴，然后通过操纵系统粘度以及表面活性剂和油相溶剂来在第二阶段拉伸这些液滴。
评估了两步 ESE 方案，其中在低粘度下形成油滴，然后通过增加水相粘度来拉伸液滴。评估了不同的表面活性剂和油相溶剂，以优化可生物降解的 PLGA 棒的产率。通过成像剂评估了棒的药物负载，并通过血流粘附测定评估了血管靶向输送应用。
两步 ESE 方法生成的 PLGA 棒的纵横比分别低至 3.2 µm 和 700 nm。氯仿和偏磷酸钠分别是用于制造亚微米棒的最佳溶剂和表面活性剂。与球体相比，棒显示出更快释放尼罗红的能力，并在体外和体内成功靶向了剪切流下的发炎内皮。
