title: Hyaluronan derivatives: Alkyl chain length boosts viscoelastic behavior to depolymerization.
abstract: Five amide derivatives of Hyaluronic Acid (HA) were synthesized with C8, C12, C15, C16 and C18 linear alkyl-amines. These polymers (Hyadd) were tested against thermal, oxidative and hyaluronidase degradation by means of rheological experiments and SEC analysis and compared to non-modified HA. First of all, no free hexadecylamine was detected in the treated samples, meaning that under these stressing conditions only cleavage of glycosidic bonds occurs. Then, viscoelastic properties were assessed during thermal degradation and their variation as a function of time was expressed by means of a decay constant k(G'): while no significant difference in the decrease rate was observed between Hyadd-C8 and Hyadd-C12, a marked stabilization of viscoelastic properties during thermal treatment was detected for Hyadd-C15, Hyadd-C16 and Hyadd-C18. On the other hand, no difference was observed between the MW decrease rate (kMW decay constant) of HA and Hyadd-C12 to-C18; the depolymerization takes place on the backbone of the polymers independently whether they are derivatized or not, but longer alkyl chains lead to higher viscoelasticity in the depolymerized products. Finally, both oxidative and enzymatic degradation were carried out analyzing the changes in elastic modulus and in dynamic viscosity: once again, the amide side chain came out with similar behavior to chemical cross-linked HA (HBC) and with improved performances respect to linear HA in terms of preservation of viscoelasticity after chain depolymerization.
authors.affiliation: Fidia Farmaceutici s.p.a., via Ponte della Fabbrica 3/A, 35031 Abano Terme (PD), Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Pavan
authors.forename: Devis
authors.initials: D
authors.lastname: Galesso
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Menon
authors.forename: Davide
authors.initials: D
authors.lastname: Renier
authors.forename: Cristian
authors.initials: C
authors.lastname: Guarise
mesh_terms: D000577:Amides / Q000737:chemistry; D055119:Elastic Modulus; D004548:Elasticity; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D058105:Polymerization; D014783:Viscosity
chemical_list: D000577:Amides; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase
keywords: Hyaluronan; Hydrophobic amide derivative; ROS depolymerization; Rheological properties