Hyaluronic Acid Derivatives Prepared in Aqueous Media by Triazine-Activated Amidation

Abstract

A method is presented for the preparation of hyaluronic acid derivatives obtained through triazine-activated amidation. A number of amines were successfully reacted with hyaluronic acid carboxyl groups using 2-chloro-4,6-dimethoxy-1,3,5-triazine as an activating species in a mixture of water and acetonitrile under neutral conditions. By varying the amount of triazine reagent, it was possible to control the degree of modification. Depending on the amine chosen, degrees of modification ranging from 3 to 20% were obtained when using 0.5 equiv of the triazine to hyaluronic acid carboxyl groups. The possibility to perform the reaction in a mixture of water and acetonitrile facilitates the introduction of a wide range of both hydrophilic and hydrophobic amines. Triazine-activated amidation appears to be a highly versatile, controllable, and relatively mild technique for modification of hyaluronic acid, and we predict that it will be useful in the design of novel hyaluronic acid based biomaterials.

Development of Multifunctional Hyaluronan-Coated Nanoparticles for Imaging and Drug Delivery to Cancer Cells

“…The preparation of HA functionalized superparamagnetic iron oxide NPs (HA-SPIONs) started from the amine containing SPION 36 by conjugating low molecular weight HA polymer (31 kDa) using 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) 37 as the coupling reagent (Figure 1). The HA-SPION was thoroughly characterized by a variety of techniques including TEM, DLS, zeta potential, TGA and HRMAS-NMR (Figure S1).…”

Development of drug loaded nanoparticles for tumor targeting. Part 1: synthesis, characterization, and biological evaluation in 2D cell cultures

“…62, 63 Naturally existing HA has molecular weight ranging from 10 kDa to 10 MDa depending on its source and purification procedures. 28 CD44 contains a single HA binding domain, which can accommodate a HA oligosaccharide up to hexasaccharide in length.…”

Enhancing hyaluronan pseudoplasticity via 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated conjugation with short alkyl moieties

“…Furthermore, the associative properties of these HA derivatives were found to be controlled by the complex balance between electrostatic repulsions and hydrophobic attractions associated with intra and interchain hydrogen bond interactions (Creuzet et al, 2006). Bergman et al reported the grafting of a series of amines including propylamine to HA using triazine-based activation chemistry (Bergman, Elvingson, Hilborn, Svensk & Bowden, 2007), however the rheological properties were not analysed.…”