Oral hyaluronic acid (HA) is a ubiquitous biopolymer that has gained attention as a treatment for local or systemic diseases. Here, we prepared and characterized structures of free HA (f-HA) with a high (>10⁵ Da), intermediate (≤10⁵ Da), and low (≤10⁴ Da) average molar mass (MM); nanoparticles crosslinked with adipic dihydrazide (n-HA); and mixed formulations (mixed-HA) containing f-HA and n-HA. MM distribution determined the structure, hydrodynamic diameter, and zeta potential of the f-HAs. Crosslinking changed the physicochemical properties in n-HA. In vitro tack adhesion assays, using mucin tablets or a viable rat intestinal mucosa, showed better mucoadhesion with f-HA (intermediate MM) and mixed-HA (25% n-HA), especially in the jejunum segment. High MM f-HA presented negligible mucoadhesion. n-HA showed the deepest diffusion into the porous of the membranes. In vivo results showed that, except for high MM f-HA, there is an inverse relationship between rheological changes in the intestinal membrane macerates resulting from mucoadhesion and the effective intestinal permeability that led to blood clearance of the structures. We conclude that the n-HA formulations are promising for targeting other tissues, while formulations of f-HA (intermediate MM) and mixed-HA are better for treating dysbiosis.

中文翻译：

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肠道中的透明质酸：结构、流变学和粘膜粘附对大鼠肠道摄取的影响


口服透明质酸（HA）是一种普遍存在的生物聚合物，作为局部或全身疾病的治疗方法而受到关注。在这里，我们制备并表征了具有高（>10 ⁵ Da）、中（≤10 ⁵ Da）和低（≤10 ⁴ Da）平均摩尔质量（MM）的游离HA（f-HA）的结构；与己二酸二酰肼（n-HA）交联的纳米颗粒；以及含有f-HA和n-HA的混合制剂(mixed-HA)。 MM 分布决定了 f-HA 的结构、流体动力学直径和 zeta 电位。交联改变了 n-HA 的物理化学性质。使用粘蛋白片或活大鼠肠粘膜进行的体外粘性粘附试验显示，f-HA（中间 MM）和混合 HA（25% n-HA）具有更好的粘膜粘附力，尤其是在空肠段。高 MM f-HA 表现出可忽略不计的粘膜粘附。 n-HA 显示出最深的扩散到膜的多孔中。体内结果表明，除了高 MM f-HA 外，粘膜粘附引起的肠膜浸渍流变学变化与导致结构血液清除的有效肠通透性之间存在反比关系。我们的结论是，n-HA 制剂有望用于靶向其他组织，而 f-HA（中间 MM）和混合 HA 制剂更适合治疗生态失调。