Abstract
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.
Highlights
Hyaluronic acid (HA) is a glycosaminoglycan ubiquitous in the human body [1]
Size spectra were recorded in terms of intensity (I) distribution that highlight all sizes present in the sample due to the signal amplification to diameter raised to the sixth power (I α d6) and the (N) distribution (N α d), where light scattering corresponds to the predominant network size (Supplementary Figures S1–S3)
We reviewed the structural changes of HA related to concentration, molar mass (MM), pH, the gastrointestinal system and the molecular dynamics of intestinal uptake and signaling, immunomodulation at intestinal and systemic levels, and HA fate in other tissues
Summary
Hyaluronic acid (HA) is a glycosaminoglycan ubiquitous in the human body [1]. HA performs biological functions at various concentrations, molar masses (MM), and size distributions of its chains structured in different spatial architectures [2,3,4,5]. The effect of multifunctional protein TSG-6 in various models of inflammation shows an alteration the structure of HA via its direct crosslinking of HA chains, enhance HA-receptor interactions and contributes to the anti-inflammatory effects. This anti-inflammatory process by an allosteric mechanism preventing simultaneous binding of HA and inhibition of interleukin-1 (IL-1), interleukin-6 and tumour necrosis factor (TNFα), and competing interactions of HA for their distinct binding sites on link_TSG6, both process are more effective with HA with high MM [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
