Bile Salts Trigger Deformability in Liposomal Vesicles through Edge-Activating Action.

Abstract

This study investigates how bile-salt-based edge activators (EAs) (sodium cholate, NaC; sodium deoxycholate, NaDC; and sodium taurocholate, NaTC) can influence the mechanical properties and deformability of liposomal vesicles. We have elucidated their effect on liposomes composed of l-α-phosphatidylcholine (SPC). Liposomes were formulated using thin-film hydration and characterized using scattering, spectroscopic, and atomic force microscopic (AFM) techniques. Our data show that bile salts can alter the hydrodynamic diameter (D_h), morphology, and mechanical characteristics of vesicles. Their effect on the deformability and Young's modulus of vesicles followed the order NaDC ≥ NaC > NaTC. Breakthrough events were noticed in the vesicles at specific depth levels during force-deformation and force-indentation experiments. Based on the lack of hysteresis in the approach-retract curve, we inferred that the vesicles attained elasticity at lower concentrations of NaDC. Hydrophobic interactions between phospholipids and bile salts were verified from Fourier-transformed infrared spectrophotometer (FTIR) experiments. Increase in bile salt concentration was accompanied by a red shift of the acyl chain (asymmetric stretching CH₂ and symmetric stretching CH₃) and phosphate groups. This shift suggests enhanced hydrogen bonding between liposomes and bile salts. The affinity of bile salts for the SPC molecule correlated with their relative hydrophobicity. We conclude that NaDC can indeed improve the mechanical properties of liposomes and their ability to penetrate biological barriers.