Synthesis and characterization of new derivatives of alginic acid and evaluation of their iron(III)-crosslinked beads as potential controlled release matrices

Abstract

Context: The excellent gelling and safety profiles of alginic acid combined, however, with drawbacks of its ionotropically crosslinked beads (i.e. their quick release of loaded drugs) prompted us to chemically modify alginic acid. Objective: Alginic acid was chemically conjugated with four amines of varying hydrophilichydrophobic properties (i.e. tris(hydroxymethyl)methyl-, allyl-, benzyl-or pentyl-amines) in an attempt to enhance the drug release profiles from respective metal crosslinked beads. Materials and methods: Chemical conjugation procedures were performed using dicyclohexylcarbodiimide as a coupling agent and the resulting new derivatives were characterized using proton nuclear magnetic resonance (1H NMR), infrared (IR) spectroscopy and differential scanning calorimetry (DSC). These modified polymers were used to prepare iron (III)-crosslinked beads loaded with folic acid as model drug, which were tested in vitro to assess their folic acid release profiles. Results and discussion: Interestingly, the resulting beads accessed enteric release kinetics, with tris(hydroxymethyl)methyl-amide alginic conjugate producing most pronounced enteric profile. Conclusion: The results suggest the possibility of achieving controlled drug release from alginate-based beads via facile chemical modification of alginic acid. © 2014 Informa Healthcare USA, Inc.