Two-step Controlled Release of Gallic Acid by Novel Phospholipid Complexes of Alkyl Gallates

Abstract:

[Objective] Alkyl gallates can interact with phospholipids to form phospholipid complexes of alkyl gallates. This study aims to investigate the sustained release of gallic acid by such phospholipid complexes. [Method] A thin-film dispersion method was employed to prepare phospholipid complexes of alkyl gallates with different acyl chain lengths. The gastrointestinal digestion and absorption characteristics of these phospholipid complexes were studied based on a rat model of everted gut sac and high-performance liquid chromatography-ultraviolet (HPLC-UV) detection. [Result] Alkyl gallates were gradually released from their phospholipid complexes (Step 1) and hydrolyzed by intestinal lipase to produce free gallic acid (Step 2). In addition, both gallic acid and short-chain alkyl gallates (methyl gallate, ethyl gallate, propyl gallate, and butyl gallate) can cross the small intestinal mucosa, and the short-chain alkyl gallates that cross the membrane were further hydrolyzed to produce free gallic acid (Step 2). As the acyl chain length increased, the hydrolysis rate constant showed a trend of first increasing (methyl gallate: 1.081×10^-5 min^-1; ethyl gallate: 1.768×10^-5 min^-1; propyl gallate: 2.193×10^-5 min^-1; butyl gallate: 2.520×10^-5 min^-1; octyl gallate: 2.901 × 10^-5 min^-1) and then decreasing (octyl gallate: 2.901×10^-5 min^-1; dodecyl gallate: 2.048×10^-5 min^-1; tetradecyl gallate: 1.136×10^-5 min^-1; hexadecyl gallate: 0.689×10^-5 min^-1; stearyl gallate: 0.409×10^-5 min^-1). [Conclusion] Therefore, by adjusting the acyl chain length of alkyl gallates, a two-step controllable sustained release of gallic acid by phospholipid complexes of alkyl gallates can be effectively achieved.