Abrami Michela, D'Agostino Ilenia, Milcovich Gesmi, Fiorentino Simona, Farra Rossella, Asaro Fioretta, Lapasin Romano, Grassi Gabriele, Grassi Mario
Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio, 6/A, I-34127 Trieste, Italy.
Soft Matter. 2014 Feb 7;10(5):729-37. doi: 10.1039/c3sm51873f.
Here we focus the attention on the physical characteristics of a highly biocompatible hydrogel made up of crosslinked alginate and Pluronic F127 (PF127). This is a composite polymeric blend we propose for artery endoluminal delivery of an emerging class of molecules named nucleic acid based drugs (NABDs). The physical characterization of our composite gel, i.e. mesh size distribution and PF127-alginate mutual organization after crosslinking, can significantly determine the NABDs release kinetics. Thus, to explore these aspects, different technical approaches, i.e. rheology, low/high field NMR and TEM, were used. While rheology provided information at the macroscopic and nano-level, the other three approaches gave details at the nano-level. We observe that Pluronic micelles, organizing in cubic ordered domains, generate, upon alginate crosslinking, the formation of meshes (≈ 150 nm) larger than those occurring in a Pluronic-free alginate network (≈ 25 nm). Nevertheless, smaller alginate meshes are still on and can just host un-structured Pluronic micelles and water. Accordingly, the gel structure is quite inhomogeneous, where big meshes (filled by crystalline Pluronic) co-exist with smaller meshes (hosting water and un-structured PF127 micelles). While big meshes offer a considerable hindering action on a diffusing solute, smaller ones represent a sort of free space where solute diffusion is faster. The presence of big and small meshes indicates that drug release may follow a double kinetics characterized by a fast and slow release. Notably, this behavior is considered appropriate for endoluminal drug release to the arterial wall.
在这里，我们将注意力集中在一种由交联藻酸盐和普朗尼克F127（PF127）组成的高生物相容性水凝胶的物理特性上。这是一种复合聚合物共混物，我们提议将其用于动脉腔内递送一类名为核酸类药物（NABDs）的新兴分子。我们的复合凝胶的物理特性，即交联后网孔尺寸分布和PF127 - 藻酸盐的相互组织，能够显著决定NABDs的释放动力学。因此，为了探究这些方面，我们使用了不同的技术方法，即流变学、低/高场核磁共振和透射电子显微镜。流变学在宏观和纳米层面提供信息，而其他三种方法在纳米层面给出细节。我们观察到，在立方有序域中组织的普朗尼克胶束在藻酸盐交联时会生成比无普朗尼克藻酸盐网络中出现的网孔（≈25纳米）更大的网孔（≈150纳米）。然而，较小的藻酸盐网孔仍然存在，并且只能容纳无结构的普朗尼克胶束和水。相应地，凝胶结构相当不均匀，其中大网孔（由结晶普朗尼克填充）与较小网孔（容纳水和无结构的PF127胶束）共存。虽然大网孔对扩散溶质有相当大的阻碍作用，但较小的网孔则代表一种自由空间，溶质在其中扩散更快。大网孔和小网孔的存在表明药物释放可能遵循以快速释放和缓慢释放为特征的双动力学。值得注意的是，这种行为被认为适用于向动脉壁的腔内药物释放。
