Efficient Synthesis of an Aldehyde Functionalized Hyaluronic Acid and Its Application in the Preparation of Hyaluronan−Lipid Conjugates

An efficient method to synthesize hyaluronan oligosaccharide lipid conjugates is described. This strategy is based on the introduction of a double bond in the glucuronic acid of the hyaluronic acid (HA), by the biodegradation of HA with hyaluronate lyase, followed by the generation of a free aldehyde group at the nonreducing end of hyaluronic acid via ozonolysis and the subsequent reduction of the generated ozonide. The resulting aldehyde-functionalized HA is then coupled to dipalmitoyl phosphatidylethanolamine (DPPE) using reductive amination chemistry. This methodology can be extended to link molecules such as biotin, polymers, or proteins to HA for numerous applications in drug delivery and in the creation of biocompatible materials for tissue repair and engineering.