Stability and pH sensitivity of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles

Abstract

The bilayer stabilization effect of sulfatide and the pH sensitivity of sulfatide-containing 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) small unilamellar vesicles were examined by light scattering and the release of entrapped calcein. At 30 mol% sulfatide, stable DOPE/sulfatide vesicles were formed at the physiological pH and their stability was preserved in the presence of human plasma. These vesicles were found to be pH-sensitive and became leaky at pH 6.0 or when there was a pH-gradient across the membrane bilayer. Under such conditions, the amount of calcein released after 24 h incubation at 37 degrees C was increased by one-fold compared to that found at pH 7.4. Our results suggest that the hydration and partial dehydration of the headgroup of sulfatide upon changing pH play an essential role in determining the pH sensitivity of DOPE/sulfatide vesicles, while the importance of the condensing effect of the glycolipid on membrane bilayer is less significant.

Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells

“…For effective intracellular drug and/or gene delivery, early release of the cargo is always desirable to avoid lysosomal degradation in clathrinmediated endocytosis. Presence of DOPE definitely reduces the chance of lysosomal degradation as the liposomes would become unstable in endosomes with an acidic pH [16,17]. Moreover, it is advantageous to have a significant portion of SCL internalized via the clathrin-independent pathway, e.g., internalization mediated by caveolae/lipid rafts in which the caveosomes could deliver their contents into other nonlysosomal subcellular compartments.…”

“…Furthermore, as the stability of this drug delivery system is pH sensitive [16,17] and its internalization by cells involves both clathrin-dependent and -independent pathways, it may have broad applications for delivery of substances such as imaging agents, therapeutic proteins and peptides directly into the cytoplasm of the target tumor cells. All these warrant further exploration.…”

“…Appropriate amounts of lipids were transferred from their respective stock solutions into glass tubes and dried by evaporation under a nitrogen stream, as described by Wu and Li [17]. The ratio of sulfatide to phospholipid was chosen such that liposomes would be formed with the optimal stability [16,17]. For fluorescence microscopy studies, 0.5 mol% of Rh-PE was included.…”

“…In other words, sulfatide, a natural acidic glycosphingolipid consisting of a hydrophobic ceramide and a hydratable galactose residue sulfated at the C3 position, is a promising candidate as the ligand of targeted carriers to deliver anticancer drugs to tumor cells via binding to TN-C. In fact, sulfatide had been chosen previously as a minor lipid component in liposomes preparation [15][16][17]. It was found that incorporation of sulfatide into phospholipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) vesicles greatly enhanced the stability of the liposomes formed, even in the presence of plasma, presumably due to hydration of the negatively charged sulfate headgroup of the glycosphingolipid [17].…”

Sulfatide-containing lipid perfluorooctylbromide nanoparticles as paclitaxel vehicles targeting breast carcinoma

“…18 Sulfatide, a nonantibody ligand, is often readily available, easy to handle, 19 and has been used as the minor lipid component of various liposomes as drug delivery vehicles. [20][21][22] Hence, sulfatide, a type of lipid, can actively incorporate with other lipids and act as a part of the outer lipid monolayer component of the targeted ligand. Based on this information, we first combined the sulfatide and NPs described above, called sulfatidecontaining lipid PFOB NPs (SNPs), for the targeted delivery of PTX to breast carcinoma cells.…”