The role of hydrophobic modification on hyaluronic acid dynamics and self-assembly

• Published in: Carbohydrate polymers Vol. 182; pp. 132 - 141
• Main Authors: Payne, William M., Svechkarev, Denis, Kyrychenko, Alexander, Mohs, Aaron M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.02.2018
• Subjects: Carbohydrate Conformation; Computer-aided formulation design; Hyaluronic Acid - chemical synthesis; Hyaluronic Acid - chemistry; Hydrodynamics; Hydrophobic and Hydrophilic Interactions; Molecular dynamics; Molecular Dynamics Simulation; Nanocarrier; Polymeric nanoparticles; Self-assembly; Structure-property relationship; Surface-Active Agents - chemical synthesis; Surface-Active Agents - chemistry; FF; CAC; SAS; Structure-property relationship; Molecular dynamics; DLS; NMR; Self-assembly; Polymeric nanoparticles; Nanocarrier; Computer-aided formulation design; Rg; MD; HA
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2017.10.054

[Display omitted] •Colloidal properties of HA-based nanomaterials result from single strand dynamics.•Results of MD simulations are supported experimentally.•Trends observed in silico are also observed in bulk solution experiments. The advent of nanomedicine has rejuvenated the need for increased understanding of the fundamental physicochemical properties of polymeric amphiphiles. Hyaluronic acid (HA) is a hydrophilic polysaccharide that is frequently conjugated to hydrophobic moieties and then used to entrap dyes and therapeutics. Here, we develop computational models to examine the effects of the hydrophobic modification on supramolecular behavior among three systematically designed HA derivatives substituted with alkyl chains of increasing length. Our simulations coalesce with experimentally obtained results to demonstrate the dependence of supramolecular behavior on intramolecular forces. We show that the formation of clearly defined hydrophobic domains in samples of octadecylamine-modified HA compared to HA conjugates with shorter alkyl chains is a result of more favorable hydrophobic interactions. Trends in hydrodynamic radius and polydispersity are observed in experimental results that coalesce with theoretical calculations, suggesting that supramolecular properties are dependent on the physicochemical characteristics of individual polymer strands.