Deconstructing lipid emulsion binding of amitriptyline: potential significance for phospholipid emulsifier

Background Lipid emulsion (LE) consists of soybean or other oil emulsified with phospholipid. We explored relative binding effects of LE, phospholipid liposomes (PLL), and soy oil (Soy).Methods We added 4 micrograms of amitriptyline to seven different 10 mL samples. Aqueous amitriptyline concentrations were measured in phosphate buffered saline (PBS) at pH 7.4 and two PBS suspensions (one at pH 7.4, one at pH 6.4) of each of 0.1% phospholipid liposomes, 2% LE, and stirred 2% soybean oil.Results Amitriptyline concentration in PBS (total amitriptyline, no sequestration (TNS) (±95% CI)) was 1300 ± 13 nmol/L. At pH 7.4, the aqueous concentration was lowest for the LE (54 ± 29 nmol/L) suspension and lower for PLL (395 ± 6 nmol/L) suspension than for Soy (632 ± 11 nmol/L). There was little change in the aqueous concentration with pH decrease for the LE (58 ± 8 nmol/L) and PLL suspensions (425 ± 15 nmol/L), and a marked increase in aqueous concentration in the Soy suspension (1260 ± 14 nmol/L).Conclusion These findings raise the possibility that electrostatic interactions in the lipid droplet micelle membrane may play a role in the binding and drug distribution effects of LE in amitriptyline toxicity.