Related Experiment Video
Updated: Jun 4, 2025

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding
Published on: March 24, 2018
Hydrophobic ion pairing: lipophilicity improvement of anionic macromolecules by divalent cation mediated complex
Sera Lindner1, Fabrizio Ricci1, René Holm2
1Thiomatrix Forschungs- Und Beratungs GmbH, Trientlgasse 65, 6020, Innsbruck, Austria.
Abstract:
The aim of this study was to develop an alternative strategy to sufficiently increase the lipophilicity of anionic model macromolecules (MM) without the use of cationic counterions. Enoxaparin (ENO), insulin (INS) and poly-L-glutamic acid (PLG) were ion paired with anionic surfactants (sodium decanoate (DEC), sodium dodecyl sulfate (SDS), sodium stearate (SS) and sodium octadecyl sulfate (SOS)), mediated by divalent cations such as magnesium, calcium and zinc. Complexes were evaluated regarding their precipitation efficiency and logDn-butanol/water. SEDDS were developed, loaded with the complexes and characterized for their size and stability. Finally, payloads and logDSEDDS/release medium were determined. Divalent cation mediated ENO, INS and PLG complexes were successfully formed as underlined by high precipitation efficiencies above 90% in case of Zn2+-mediated complexes. Most pronounced increase in logDn-butanol/water was achieved for ENO-Zn2+-SOS (1.85), INS-Zn2+-SOS (0.80) and PLG-Zn2+-SS (0.48) providing suitable solubilities in commonly used SEDDS components. Developed SEDDS displayed droplet sizes below 200 nm without major changes after loading with MM complexes. Payloads up to 18.72 mg/ml could be achieved in developed SEDDS for ENO-Zn2+-SOS, and 2.44 mg/ml and 6.93 mg/ml for INS-Zn2+-SOS and PLG-Zn2+-SS, respectively. In general, highest lipophilicity enhancement and thus solubility in SEDDS was obtained with Zn2+-mediated complexes among the investigated cations and particularly with the highly negatively charged polysaccharide ENO. The formation of complexes between anionic MM and anionic surfactants mediated by divalent cations, substituting normally used cationic counterions exhibiting higher toxicity, offers a promising alternative to enhance their lipophilicity for oral drug delivery.
Related Concept Videos
Intermolecular Forces
Complexation Equilibria: Factors Influencing Stability of Complexes
Formation of Complex Ions
Complexation Equilibria: The Chelate Effect
Pore Transport and Ion-Pair Transport
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Aqueous Solutions and Heats of Hydration
When ionic compounds dissolve in water, the ions in the solid separate and disperse uniformly throughout the solution because water molecules surround and solvate the ions, reducing the strong electrostatic forces between them. This process...

