Aggregation Behavior of Pegylated Bile Acid Derivatives

Abstract

Bile acids are amphiphilic endogenous steroids that act as anionic surfactants in the digestive tract and aggregate in aqueous solutions. Nonionic surfactants were synthesized by grafting poly(ethylene glycol) chains of various lengths (pegylation) to three bile acids (lithocholic, deoxycholic, and cholic acid) using anionic polymerization. The aggregation properties of the derivatives were studied with viscosity measurements and light scattering as well as with steady-state and time-resolved fluorescence techniques, and the aggregates were visualized by transmission electron microscopy to elucidate the effect of pegylation on the aggregation process. The fluorescence results showed a good correlation with the capacity of the bile acid derivatives to solubilize a hydrophobic drug molecule. The solubilization of ibuprofen depends on the length and the number of grafted PEG chains, and the solubilization efficiency increases with fewer PEG chains on the bile acid. The results indicate their potential for use in the design of new bile acid-based drug-delivery systems.

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release

“…The ethanolamine derivative of cholic acid with four hydroxyl groups was synthesized according to a previous method. 45,46 For anionic polymerization, 5β-cholanoamide (1.66 mmol, 0.75 g) was dissolved in 40…”

“…We have previously shown the advantage of using bile acids in the design of drug delivery systems. [40][41][42] Micelles formed by bile acid-based polymers are less densely packed than linear polymers of similar structure, 43 creating an internal reservoir that may hold a larger amount of hydrophobic therapeutic molecules. We have studied the loading of hydrophobic itraconazole in bile acid-based nanoparticles.…”

Polymers made of bile acids: from soft to hard biomaterials

“…Le Dévédec et al studied the aggregation behaviour of three different bile acids functionalized with PEG, i.e., lithocholic acid (LCA), deoxycholic acid (DCA), and CA, and their encapuslation efficiencies toward the hydrophobic drug ibuprofen. 32 The three different bile acids used in their study present varying numbers of hydroxyl groups, which permits different numbers of PEG chains to extend from the steroid core: two for LCA, three for DCA, and four for CA. By varying the numbers of PEG arms and their relative length, the hydrophobicity of the system was varied and the impact of this parameter on the drug loading efficiency was determined and optimized.…”

Differential Perturbation of the Protrotropic Equilibrium of a Biological Photosensitizer within Bile Salt Aggregates of Varying Hydrophobicity: A Fluorimetric Investigation

“…Unlike conventional surfactants, the bile salt molecules have a convex hydrophobic surface along with a concave hydrophilic surface in the basic steroidal skeleton with a supple tail connected to it, which differs from a typical detergent . Consequently, the aggregation process of the bile salts proceeds continuously over a wide range of concentration due to their much lower aggregation numbers which in fact is a proliferation of their rigid structure . The most recognized model enlightens that bile salts form primary aggregates generally at low concentration impelled by the hydrophobic interaction of the convex face of the monomeric units.…”