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

Abstract

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 one 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.

Challenges in Development of Nanoparticle-Based Therapeutics

“…Each of these systems may be unstable due to high-surface free energy and the tendency to aggregate. The use of amphipathic PEG on the surface can inhibit liposome aggregation by reducing interfacial free energy with water and acting as a steric barrier, therefore improving stability in addition to extending in vivo circulation half-life of liposomes ( 46 – 48 ). The physical stability of liposome drug products is determined by the integrity, size distribution, and composition of liposome vesicles.…”

Biomimetic Glycoliposomes as Nanocarriers for Targeting P-Selectin on Activated Platelets

“…To explore new therapeutic strategies for inflammatory diseases based on using biomimetic glycoliposomes, we have synthesized a SuLe a glycolipid 1 (designated as SuLe a -DSGA, Figure ) by conjugating SuLe a with 1,2-distearoyl- rac -glyceroglutaric acid (DSGA). SuLe a -DSGA has been incorporated into liposomes for studying vesicle size and stability ( , ). However, PSGL-1 is a thin, highly extended molecule with an average length of 54 nm.…”

“…The synthesis of 9 was based on the conjugation of our previously developed intermediate, a protected amino derivative of SuLe a 3 with DSPE-PEG-NHS 4 (with PEG Mw of 2000 and an activated carboxylic group by N -hydroxylsuccinimide), followed by deprotection of p -methoxybenzyl [Bzl(OMe)] groups, 3‘-sulfatation, and deprotection of allyl (All) and benzyl (Bzl) groups ( , ). In the natural form, Lewis antigens are attached through their reducing ends to lipids and/or proteins.…”

Preparation and Physicochemical Properties of Lauroyl‐Glutamyl‐Lysil‐Lauroyl‐Glutamate Vesicles

“…It is well known that the stability, particle size and shape of vesicles depend on turbidity [15] and zeta potential [16]. The turbidity and zeta potential of the C 12 -GLG-C 12 solution were measured with different citric acid concentrations.…”

“…DLS measurements have enabled us to examine the stability of vesicles by measuring the behavior of particle size and zeta potential within a time-course [16]. Table 2 shows the effect of time on mean diameter and zeta potential.…”