Hydrophobically modified alginate for drug delivery systems

Hydrophobically modified alginate (HMA) was synthesized by an amide coupling reaction with alkyl amine (C₈) at low pH. At and above a critical concentration, HMA forms reversible physical gel in aqueous media due to hydrophobic interactions. Unreacted guluronic units of alginate were further crosslinked with divalent cations, such as Ca²⁺, which resulted in a gel having elastic moduli ~100 kPa. Interplay of the two different gelation mechanisms, hydrophobic association and chemical crosslinking, enables us to tune the mechanical properties of the system. Solubility of a model lipophilic drug (Sulindac) was found to be improved at least by a factor of 5 compared to neat polymer, presumably due to preferential uptake of the drugs by micelles formed by hydrophobic moiety. Controlled and extended release of sulindac was observed for upto 5-6 days, probably due to stronger crosslinked alginate units surrounding the drug loaded hydrophobic rich domains.