Molecular interactions in reverse hexagonal mesophase in the presence of Cyclosporin A.

The present work investigates the detailed molecular structure of the H(II) mesophase of GMO/tricaprylin/phosphatidylcholine/water system in the presence of hydrophobic model peptide Cyclosporin A (CSA) via ATR-FTIR analysis. The conformation of the peptide in the hexagonal mesophase, as well as its location and specific interactions with the components of the carrier, were studied. Incorporation of phosphatidylcholine to the ternary GMO/tricaprylin/water system caused competition for water binding between the hydroxyl groups of GMO and the phosphate groups of the phosphatidylcholine (PC) leading to dehydration of the GMO hydroxyls in favor of phospholipid hydration. Analysis of CSA solubilization effect on the H(II) mesophase revealed a significant increase in the strength of hydrogen bonding with surfactant hydrogen-bonded carbonyls, indicating interaction of the peptide with the CO groups of the surfactants. The peptide probably caused partial replacement of the intramolecular hydrogen bonds of the mesophase carbonyl groups with intermolecular hydrogen bonds of these carbonyl groups with the peptide. Furthermore, analysis of the Amide I' peak in the FTIR spectra of the peptide demonstrated that two pairs of its internal hydrogen bonds are disrupted when it is incorporated. The partial disruption of the internal hydrogen bonds seems to cause an outward rotation of the peptide amide groups involved, resulting in more efficient intermolecular hydrogen-bonding ability. Apparently, this conformational change increased the hydrophilic properties of CSA, even making it susceptible to a weak interaction with the GMO hydroxyl groups in the interfacial region.