Recent Progress in Macromolecular Design and Synthesis of Bile Acid‐Based Polymeric Architectures

Abstract

Macromolecular engineering presents a pleasant tactic for planning the construction of desired molecular architectures from nano to macro configurations. The mechanistic pathways and synthetic features of macromolecular designs mostly rely on the precursor composition, topology, functionality, and complexity in architectures. Specifically, macromolecular design with biomolecular conjugation has attracted remarkable attention due to its typical biochemical and physiological affirmative traits. In this review article, it is intended to highlight the major progress on the macromolecular designs and synthesis of polymers comprising bile acid (BA) as the biomolecular colleague. BAs are steroidal biocomposites, produced through cholesterol metabolism in the bile of mammals and vertebrates. They are low priced, biocompatible, abundant, trivially toxic, and structurally unique for facewise amphiphilicity, which make them suitable for designing BA-based polymers (BAPs) to be utilized in biomedical fields. The major aim of this review article is to summarize the recent progress (2015-present) on the requisite necessity of BA in BAPs toward design and synthetic avenues. In particular, the design of various polymers with primary and secondary BAs at side chain, main chain, chain end, crosslinking zone, and core confined area are illustrated in this review article via numerous reported methods.

Self-assembled PHEA-based block copolymers for the synthesis of gold nanoparticles

“…1,2 Cholesterol and cholic acid have been incorporated into many polymeric systems and used in biomedical applications, such as drug delivery, antimicrobial agents, protein recognition, cell imaging, and vaccines. 3–9 Cholesterol forms part of the animal cell membranes and is a precursor for the synthesis of bile salts, sex hormones, and vitamin D. Moreover, its functions in the human body are to build and repair cell membranes, and control/modify the fluidity and permeability of the membrane. 3 Cholesterol is a critical component of the lipid layer of several liposomal systems approved by the FDA, for instance, the liposomal formulation of the COVID-19 vaccines.…”

Facially Amphiphilic Skeleton-Derived Antibacterial Cationic Dendrimers

“…Host defense peptides (HDPs) exert rapid and broad-spectrum antibacterial activity and avoid harming host cells as well as reduce the potential for inducing drug resistance. HDPs tend to segregate a so-called “facially amphiphilic” structure, in which the hydrophilic cationic and hydrophobic residues are facially located on their secondary structures and facilitate the direct membrane disruption of bacteria. − Synthetic polymers have been designed to mimic the activity of HDPs, and one of the most challenging topics is how best to spatially arrange the cationic and hydrophobic residues to form a facially amphiphilic structure within the macromolecular architecture. − Bile acids (BAs), such as cholic acid (CA) and lithocholic acid (LCA), derived from cholesterol in mammals, have a rigid skeleton of four condensed rings and multiple functional groups. − Along with excellent biocompatibility, the hydroxyl groups of CA and polycyclic hydrocarbon structures are located on the α and β surfaces of the rigid skeleton, respectively, and form a rare facially amphiphilic structure similar to HDPs, − promoting a selective localization and penetration into bacterial membranes − and making BAs suitable blocks for designing antimicrobials. ,, In the past decades, by utilizing facially amphiphilic skeletons of BAs, there have been extensive efforts in the development of BA-based antimicrobials in which facially amphiphilic BA skeletons are usually conjugated with some positive segments. − For example, Savage et al − converted the three hydroxyl groups on CA into three flexible primary amine groups . In contrast, to reduce the residual toxicity of small molecules and increase the density of cationic charges, the Tang group , designed a series of antibacterial macromolecules bearing CA quaternary ammonium pendants.…”