Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Graduate School of Science, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan.
Int J Pharm. 2021 Jun 1;602:120599. doi: 10.1016/j.ijpharm.2021.120599. Epub 2021 Apr 20.
Previously, we reported the formation of 100-200 nm disk- and tube-like nanoparticles by hydration of -ascorbyl 2,6-dipalmitate (ASC-DP) and distearoylphosphatidylethanolamine polyethylene glycol 2000 (DSPE-PEG) films prepared at an initial molar ratio of 2:1. This study investigated the feasibility of nanoparticle formation with higher ASC-DP loading. Although particle size distribution determined by dynamic light scattering showed a multimodal pattern including micro-sized particles at a molar ratio of 3:1, the mean particle size gradually decreased with a further increased molar ratio. Homogeneous ca. 240 nm nanoparticles with a unimodal size distribution were obtained at a molar ratio of 10:1. FE-TEM showed that the nanoparticles at a molar ratio of 10:1 were rod-shaped with a diameter of ca. 100 nm and a length of ca. 300 nm. After centrifugation, X-ray analysis of the nanoparticle precipitates showed that these rod-like nanoparticles were composed of a series of lamellar structures with 3.7 nm repeated units. The molar ratio of ASC-DP/DSPE-PEG in the nanoparticle precipitates determined by H NMR measurements was 68.8:1. The rod-like nanoparticles should be composed of a core-shell structure, where a small amount of DSPE-PEG covers the lamellar structure of ASC-DP. Further increase in the ASC-DP/DSPE-PEG molar ratio over 33:1 no longer provided nanoparticles. Hence, to prepare a stable ASC-DP nanoparticle suspension, it is necessary to prepare ASC-DP/DSPE-PEG films containing at least 3 mol% DSPE-PEG.
先前,我们曾报道过通过 -抗坏血酸 2,6-二棕榈酸酯(ASC-DP)和二硬脂酰基磷脂酰乙醇胺聚乙二醇 2000(DSPE-PEG)薄膜在初始摩尔比为 2:1 的条件下水化形成 100-200nm 的盘状和管状纳米粒子。本研究考察了高 ASC-DP 负载下形成纳米粒子的可行性。尽管动态光散射法测定的粒径分布呈现出多峰模式,包括摩尔比为 3:1 时的微尺度粒子,但随着摩尔比的进一步增加,平均粒径逐渐减小。在摩尔比为 3:1 时,粒径分布呈单峰模式,粒径约为 240nm 的均匀纳米粒子。FE-TEM 显示,在摩尔比为 10:1 时,纳米粒子为棒状,直径约为 100nm,长度约为 300nm。离心后,对纳米粒子沉淀物进行 X 射线分析表明,这些棒状纳米粒子由一系列具有 3.7nm 重复单元的层状结构组成。通过 H NMR 测量确定的纳米粒子沉淀物中 ASC-DP/DSPE-PEG 的摩尔比为 68.8:1。棒状纳米粒子应由核壳结构组成,其中少量的 DSPE-PEG 覆盖 ASC-DP 的层状结构。当 ASC-DP/DSPE-PEG 的摩尔比超过 33:1 时,不再提供纳米粒子。因此,为了制备稳定的 ASC-DP 纳米粒子悬浮液,有必要制备至少含有 3mol% DSPE-PEG 的 ASC-DP/DSPE-PEG 薄膜。