Self‐aggregated nanoparticles composed of periodate‐oxidized dextran and cholic acid: preparation, stabilization and in‐vitro drug release

Abstract

A novel method was used to synthesize cholic acid hydrophobic-modified dextrans (CAH-Dex) which form nanoparticles in aqueous solution. The stabilization and drug-loading of the formed nanoparticles were investigated. Dextran was oxidized by sodium periodate to dextran dialdehyde which was then conjugated with cholic acid hydrazide through an acyl hydrazone linkage. The self-aggregation behavior of the resulting conjugates was investigated using nuclear magnetic resonance, fluorescence and photo correlation spectrometry. The conjugates were found to have low critical aggregate concentrations (CAC) (0.46-0.96 × 10 −2 mg mL −1 ) which is characteristic, depending on both the oxidization and substitution degrees. Above the CAC the conjugates tend to form nanoparticle aggregates with inner hydrophobic environment. The diameters of the nanoparticles rely on the pH of the medium due to the aldo-enol transition of the dextran dialdehyde. By crosslinking the aldehyde groups located on the surface using adipic dihydrazide, the nanoparticles were obviously stabilized. The drug-loading and release behavior of the nanoparticles was investigated using indomethacin as a hydrophobic model drug.

Poly(p‐phenylene ethynylene)s with Facially Amphiphilic Pendant Groups: Solvatochromism and Supramolecular Assemblies

“…The thickness of the cholate unit is about 0.5 nm [20c] and the distance between p-stackings of PPE is estimated as about 0.4 nm. [22] It has been generally recognized that bile acid derivatives tend to assemble in a headto-tail fashion with two distinguishable faces of the cholates tilted up and down alternately, [20] whereas PPE derivatives with long alkyl or alkoxy groups were expected to form a lamellar or doubly lamellar morphology in which the structure of the polymer is dominated by side-chain packing. [23] Based on the data and results described above, we proposed that the molecular packing in the membrane of the formed vesicular structure has a multilayer lamellar structure through a combination of hydrogen bonding, hydrophobic interaction, and p-p stacking, in which the conjugated molecule is arranged in a highly organized pattern and the bile acid units are in an antiparallel interlocked configuration (Figure 8b).…”

“…[20] The mechanism of their formation is quite complex and often involves complicated "secondary assemblies". Figure 8a summarizes the aggregation behavior of cholic acid decorated PPE, which shows different buildups of supramolecular assemblies dependent upon the conditions used.…”

Synthesis and antimicrobial activity of cholic acid hydrazone analogues

“…Very recently there are two reports of antimicrobial activity of cholic acid derivatives [3,4,18,19]. Willemen et al reported that the antimicrobial activity of cholic acid against Escherichia coli and Enterobacter faecalis could be enhanced through introducing the cationic trimethylammonium groups [20].…”

Biomaterials made of bile acids

“…Polymers can be modified to introduce -CHO groups, followed by derivation with bile acids (Figure 10) [59][60] .…”

“…Bile acids are often attached as pendent groups to polysaccharides (chitosan [50][51][52] , glycol chitosan [53][54][55][56] , heparin [57] , dextran [58][59][60] or cellulose [61] ) or proteins (bovine serum albumin) [62,63] via ester or amide bonds (Figure 9) [64] . Polymers can be modified to introduce -CHO groups, followed by derivation with bile acids (Figure 10) [59][60] .…”