Targeted delivery of peptidoglycan immunomodulators using liposomal carriers: NMR study of the lipid encapsulation.

FERNANDO E. CHAIN; R. RIBIć; D. SINNAEVE; J. C. MARTINS; S. TOMIć; K. FEHÉR

Spa

Simposio; 13th Young Belgian Magnetic Resonance Scientist; 2014

Université de Mons

Peptidoglycan (PGN) as well as fragments and substances derived from it, have well-documented immunomodulating properties[1] exerted by interaction with innate immune receptors. Such immunomodulators are urgently needed in many medical interventions[2], such as adjuvants in vaccines or in aiding cancer therapies. In order to selectively modulate a certain subset of immune cells using PGN fragments, we have developed actively targeted delivery of PGN-based immunomodulants using liposomes as carriers. We have investigated the encapsulation of targeting compounds into lipid bilayers and the interaction between them on a molecular level using NMR spectroscopy. We have shown that the PGN derivatives are incorporated in the studied lipid bilayers by the change of the sign and intensity of the nOe as well as by the observation of slower translational diffusion in PFG-NMR spectra. We have determined the encapsulation efficiency and have found that the chirality of the adamantly group attachment had a large influence on the entrapment efficiency. We have utilised STD experiments for the characterisation of the orientation of the studied derivatives in the bilayer. We have found that the adamantyl group does penetrate the lipid core of the bilayer and acts as an anchor of the PGN derivative cargo, while the hydrophilic peptidoglycan fragment is exposed on the surface.