Cationic β-lactoglobulin nanoparticles as a bioavailability enhancer: comparison between ethylenediamine and polyethyleneimine as cationizers

Cationic β-lactoglobulin (CBLG) was synthesized by two strategies: extensive conjugation of ethylenediamine (EDA) and limited cationization with polyethyleneimine (PEI). Both methods provided CBLG with satisfactory water solubility and resistance to peptic digestion. Compared with EDA-derived CBLG (C-EDA), PEI-derived CBLG (C-PEI) exhibited a higher zeta potential (54.2 compared to 32.4mV for C-EDA), which resulted in significantly elevated mucoadhesion (439% and 118% higher than BLG and C-EDA, respectively) in a quartz crystal microbalance (QCM) study. In addition, PEI caused reduced conformational disruption on BLG compared to EDA as evidenced by FTIR measurement. This character, together with the steric hindrance provided by PEI, caused a phenomenal reduction in tryptic digestibility by at least 75% compared to C-EDA. In the presence of aqueous acetone, C-PEI aggregated spontaneously into nanoparticles with average size of 140 nm and narrow size distribution. These merits made C-PEI a useful material that provides desirable solubility and protection for orally administrated nutraceuticals or drugs.