Urethane-containing cationic gemini surfactants with amphiphilic tails: novel near-neutral protein carriers with minor effects on insulin structure

Three novel cationic gemini surfactants having urethane bonds as well as polyethylene glycol (PEG) block in either chain were synthesized and characterized. They differ in the number of methylene units in the spacer and are referred to as Cn-surfactants (n: 2, 4, and 6). The surfactants and their complexes with insulin, as a model protein, were extensively studied by conductometry, fluorescence spectroscopy, far-/near-UV circular dichroism (CD), and light scattering measurements. Results show that (i) the formation of surfactant-protein complex is spontaneous; (ii) the binding affinity decreases with increasing the spacer length; (iii) the electrostatic interactions are predominant in the binding process; (iv) the microenvironment around tyrosines becomes less polar with increasing surfactant concentrations; (v) the C-6-surfactant has a considerable stabilizing effect on protein secondary structure; (vi) the C-4-surfactant features an enhancing effect on insulin quaternary structure; (vii) the structural changes in the protein proceed through multiple intermediates between the initial and final states; (viii) the charged portions on micelles as well as surfactant-insulin complexes are shielded by PEG components; and (ix) the long-term storage stability of the systems is due to the steric stabilization provided by PEG chains. This is the first report of quaternary ammonium-based gemini surfactants which feature amphiphilic character in their tails. The study was conducted with a certain emphasis on their application as protein carriers. Because of the nature of the surfactants, the achievements of this applied study are also unique. Altogether, the observations indicate that these novel gemini surfactants could be considered as promising candidates for protein delivery systems.

Automated summary

In this study, three novel cationic gemini surfactants with urethane bonds and polyethylene glycol (PEG) blocks were synthesized and characterized. The surfactants were found to have significant effects on the stability and structural changes of insulin, with potential applications as protein delivery systems.