Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

Abstract

Hydrophobic ion pairing has emerged as a method to modulate the solubility of charged hydrophilic molecules ranging in class from small molecules to large enzymes. Here we review the application of hydrophobic ion pairing for encapsulating charged hydrophilic molecules into nanocarriers.

Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring

“…This difference might be caused by the larger molecular volumes of HL and CL, indicated also by outcomes of hemolysis studies, resulting in steric hindrance of the side chains of the attached surfactant molecules and thus, preventing a shielding of the residual INS charges. 3,36 Determination of Log P n-butanol/water of Insulin-Surfactant Complexes Drug-surfactant complexes prepared by HIP can be incorporated into nanocarrier systems to enable an enhanced mucus permeation as well as drug absorption, protection against presystemic drug metabolism and increased bioavailability. However, to achieve a high payload within these carriers and to minimize burst release, a distinct lipophilicity of ion pairs is key.…”

“…By using surfactants as counterions, the hydrophobicity of charged small-and large-molecular drugs can be tremendously increased due to masking of the drugs present charge and coating of its surface by the lipophilic surfactant tails. 3 Thus, HIP facilitates the incorporation of hydrophilic drugs like insulin (INS) into lipidbased nanocarrier systems enabling an oral application with increased bioavailability. 4e7 As in particular cationic surfactants exhibit high toxicity, however, their applicability is limited.…”

“…12 Accordingly, choosing an appropriate counterion for HIP is key due to its influence on the lipophilicity of the resulting ion pair. 3 For instance, partition coefficients between n-octanol and water of zero were observed when INS was complexed with sodium oleate or sodium deoxycholate, whereas a log P of 1.9 was achieved when using docusate as counterion. 7,13,14 Dai et al further increased the lipophilicity of INS by ion pairing with sodium dodecyl sulfate, as a partition coefficient of 2.6 was determined for this complex.…”

Synthesis and structural characterization of CO2-soluble oxidizers [Bu4N]BrO3 and [Bu4N]ClO3 and their dissolution in cosolvent-modified CO2 for reservoir applications

“…This approach is similar to the hydrophobic ion pairing (HIP) strategy that has been employed for drug delivery and protein solubilization in organic media where a charged hydrophilic molecule of interest is paired with a hydrophobic ion of opposite charge. [12][13][14][15][16] The bromate anion electrostatically coupled to an organic cation could potentially be solubilized in CO 2 . In general, CO 2 does not solubilize compounds that are high molecular weight, polar, or ionic to a signicant extent.…”

Antiviral Activity of Nanomaterials against Coronaviruses

“…These systems not only preserve the reliability of antigens toward degradation but also stabilize a large number of therapeutic agents such as peptides, proteins, and nucleic acids. [ 9 ]…”