Vesicle size and stability of biomimetic liposomes from 3'-sulfo-Lewis a (SuLea) containing glycolipids.

We report on the use of a natural Lewis type saccharide ligand, 3'-sulfo-Lewis a (SuLe(a)) for glycocalyx-mimetic surface modification of liposomes. Two SuLe(a)-containing glycolipids, monovalent SuLe(a)-lipid and trivalent SuLe(a) (TSuLe(a))-lipid, were synthesized, and used with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol to prepare unilaminar vesicles (ULVs) by a freeze-thaw and extrusion method. The effects of the glycolipid concentrations and the pore sizes of extrusion membranes on vesicle size and stability were investigated by photon correlation spectroscopy (PCS). Glycoliposomes, with 5% SuLe(a)- or TSuLe(a)-lipids obtained by 50 nm extrusion, had 25-30% more vesicles less than 100 nm in diameter compared with the 100 nm extrusion. TSuLe(a)-liposomes always produced larger vesicle size than SuLe(a)-liposomes, which we attribute to the larger TSuLe(a) headgroup. Both SuLe(a)- and TSuLe(a)-liposomes increased their vesicle size with increasing glycolipid concentration from 5% to 15%, and demonstrated good stability at room temperature for over 1 month. Further increasing the glycolipid concentration to 20% resulted in large vesicle aggregation after 5 days for TSuLe(a)-liposomes, while the SuLe(a)-liposomes remained stable for 10 days. SuLe(a)- and TSuLe(a)-liposomes with 15% glycolipids demonstrated better stability due to the electrostatic effect from the negatively charged SuLe(a) and TSuLe(a) headgroups. The results indicate that the biomimetic liposomes with SuLe(a)- and TSuLe(a)-lipids with 5 to 15% incorporation are sufficiently stable for the potential applications in targeted drug delivery.