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.