Polyelectrolytes are of increasing interest in delivery applications involving charged and peptide drugs due to their ability to form polyelectrolyte complexes (PECs). Drug delivery systems composed of these complexes can avoid the need for chemical crosslinking while achieving desired physicochemical properties and maintaining high biocompatibility. Natural biomaterials such as cellulose and curdlan are extremely attractive for this application due to renewability, biocompatibility and non-toxicity. Chemical modifications of cellulose to append ionic and pH sensitive groups is a promising route to novel delivery biopolymers. However, extensive introduction of highly charged groups to polysaccharide backbones is challenging due to charge repulsion and basic reaction conditions.<br/>We have utilized olefin cross metathesis as a synthetic strategy to eliminate the impediment of charge repulsion to synthesis of cellulose based polyelectrolytes. Olefin cross metathesis (CM) has proven to be a mild and efficient synthetic approach to impart a wide range of functionality to both cellulose esters and ethers. We have been able to utilize this strategy to fully modify cellulose and curdlan (DS 3) with pH-responsive carboxyl groups that permit strong polymer-drug interactions. We expect these interactions to lead to the enhancement of drug solubility and bioavailability. The high functional group tolerance of CM has allowed us to reach the maximum charge content possible in both cationic (quaternary ammonium) and anionic (carboxylate) polyelectrolytes with promise for controlled release of charged and poorly soluble drugs through the formation of polyelectrolyte complexes. This method also allows us to probe the structure-property relationships between chain length and morphology of highly charged polysaccharides. We report the synthesis, characterization and physical properties of these hypercharged polymers and initial findings of their potential in PEC drug delivery systems.

Charging up cellulose and curdlan: Expanding the potential of polysaccharide based polyelectrolytes for therapeutic delivery applications

255th National Meeting (2018)

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