Physical characterization of alginate-Pluronic F127 gel for endoluminal NABDs delivery
Physical characterization of alginate-Pluronic F127 gel for endoluminal NABDs delivery
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DOI：
10.1039/c3sm51873f
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发表时间：
2014-01-01
期刊：
影响因子：
3.4
通讯作者：
Grassi, Mario
中科院分区：
文献类型：
--
作者：
Abrami, Michela;D'Agostino, Ilenia;Grassi, Mario
在这里，我们把注意力集中在由交联藻酸盐和Pluronic F127（PF 127）组成的高度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，我们建议动脉腔内输送一类新兴的分子命名为核酸为基础的药物（NABD）。我们的复合凝胶的物理表征，即交联后的筛目尺寸分布和PF 127-藻酸盐的相互组织，可以显著地确定NABD释放动力学。因此，为了探索这些方面，使用了不同的技术方法，即流变学、低/高场NMR和TEM。流变学提供了宏观和纳米级的信息，而其他三种方法则提供了纳米级的详细信息。我们观察到，Pluronic胶束，在立方有序域组织，生成，海藻酸盐交联后，形成的网格（约150 nm）大于那些发生在Pluronic无海藻酸盐网络（约25 nm）。然而，较小的藻酸盐网格仍然存在，并且只能容纳非结构化的Pluronic胶束和水。因此，凝胶结构是非常不均匀的，其中大的网格（由结晶Pluronic填充）与较小的网格（容纳水和非结构化的PF 127胶束）共存。虽然大网格提供了相当大的阻碍作用扩散溶质，较小的代表一种自由空间，溶质扩散更快。大小网孔的存在表明药物释放可能遵循以快速和缓慢释放为特征的双重动力学。值得注意的是，这种行为被认为适合于腔内药物释放到动脉壁。
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 (approximate to 150 nm) larger than those occurring in a Pluronic-free alginate network (approximate to 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.