Formulation of hyaluronan grafted with dodecanoic acid as a potential ophthalmic treatment

Abstract

This work concerns the chemical modification of medium molecular weight hyaluronan for ophthalmic applications. The synthesis of amphiphilic HA with dodecanoyl moities was carried out under mild aqueous conditions. Perfect control of the degree of substitution was obtained by varying the molar ratio of activated fatty acid used in the reaction feed. Moreover, the preparation of the derivatives was optimized to achieve the desired degree of substitution (DS = 9.0 ± 0.2 %). The prepared hyaluronan derivatives were water-soluble and exhibited self-associating properties (amphiphilicity). The structure of the prepared derivatives was elucidated by NMR spectroscopy, rheology, turbidity, SEC-MALLS, and gas chromatography (GC). The hydrophobic moieties increase the solution viscosity by physical crosslinking. Low concentration of HAC12 is needed to prepare highly viscous solutions with potential use for ophthalmic applications. Amphiphilic HA kept the biocompatibility of hyaluronan. The degree of substitution and Mw of the amphiphilic HA controls the sterilization by filtration. The protection against desiccation was tested using human keratinocytes (HaCaT) cells lines.

Keywords: Dry eye disease; Hyaluronic acid; Hydrophobized hyaluronan; Rheology.