Innovative process for facile dextran-bovine serum albumin conjugate synthesis: Mechanism, kinetics, and characterization

Three process variations are developed to synthesize dextran-bovine serum albumin (BSA) model conjugate through the Maillard reaction and a Schiff base-Amadori solid phase rearrangement mechanism at 90 °C. The influences of lyophilization pH and dextran:BSA molar ratio on the reaction are investigated, with the highest yields achieved by absorbing heat evenly and continuously removing the water by-product under vacuum. Lyophilizing at pH 7.8 provides higher yields than materials lyophilized at pH 5.9, a result attributed to higher reactivity of deprotonated amine at pH 7.8. The purified dextran-BSA conjugate solution is heated to above the BSA denaturation temperature (80 °C) at pH 5.2 to form nanogels with a hydrodynamic diameter of 195-400 nm, with the size dependent on the conjugate composition estimated by bicinchoninic acid protein and glycoprotein carbohydrate assays.