Laurate modified low molar mass sodium hyaluronan association and solubilization efficiency in aqueous media
Abstract
A low molar mass (15000 g/mol) sodium hyaluronan (HA) was partly acylated with lauroyl groups by using the methodology of mixed anhydride acylation in aqueous organic solvents (1:1 by volume). Enzymatic degradation-based structural analyses showed no significant differences in substitution patterns of derivatives prepared in the presence of different organic co-solvents, in contrast to the results obtained earlier for both oleoyl and lauroyl hyaluronans.
In purely aqueous solutions, lauroyl hyaluronans spontaneously formed colloidal particles of hydrodynamic diameters of the order of 102 nm. For example, the derivative prepared in aqueous 1,4-dioxane (HA LA-Diox) formed relatively well-defined colloidal particles with hydrodynamic diameters from 200 to 400 nm. However, when dissolved in saline (aqueous NaCl, 9 g/L), the derivatives formed colloidal particles with hydrodynamic diameters smaller than 80 nm. A pyrene solubilization efficiency (measured by fluorimetry) in saline was found to be 3 to 8 times higher than in the aqueous solution of the same derivative. This difference can be explained by the increased ionic strength of the solution, which decreases intra-chain electrostatic repulsions of charged monomeric units, thus reducing the chain backbone stiffness.
Slightly different properties of HA lauroyl derivatives prepared with different organic co-solvents can be explained by the kinetics of acylation reaction resulting in some differences in the distribution of extent of acylation between derivative macromolecules. Solutions of all prepared HA derivatives at concentrations up to 1 g/L were found to be non-cytotoxic.