Leveraging phosphatidylcholine–alkyl gallate interactions: the role of acyl chain length in governing the two-step release of gallic acid

BACKGROUND Alkyl gallates (A-GAs) are widely used as antioxidants but suffer from poor oral bioavailability. This study investigates whether complexation with phosphatidylcholine (PC) can enable a controlled two-step release of gallic acid (GA) from A-GAs, and how the acyl chain length of A-GAs modulates this process. RESULTS PC complexes with A-GAs (methyl to stearyl gallates) were prepared by thin-film dispersion. FTIR, UV, and 1 H-NMR confirmed hydrogen bonding between the phenolic hydroxyl of A-GAs and the phosphate group of PC. In an everted rat gut sac model, short-chain A-GAs (C1–C4) and GA showed efficient intestinal permeation. The hydrolysis of A-GAs to GA followed first-order kinetics. As the acyl chain length increased, the hydrolysis rate constant ( k DH ) first increased (methyl: 0.9681 × 10 −5 min −1 ; ethyl: 1.278 × 10 −5 ; propyl: 1.852 × 10 −5 ; butyl: 1.905 × 10 −5 ; octyl: 3.154 × 10 −5 ) and then decreased (dodecyl: 1.699 × 10 −5 ; tetradecyl: 0.9911 × 10 −5 ; hexadecyl: 0.6323 × 10 −5 ; stearyl: 0.4074 × 10 −5 ). Octyl and longer esters were not transported across the intestinal mucosa due to self-association. CONCLUSION PC–A-GA complexes enable a two-step sustained release of GA: release of intact A-GAs, followed by enzymatic hydrolysis to GA. The release kinetics can be tuned by varying the acyl chain length of the A-GA, providing a rational design strategy for improving the oral bioavailability of phenolic compounds. © 2026 Society of Chemical Industry.