Glycosaminoglycan-Mediated Selective Changes in the Aggregation States, Zeta Potentials, and Intrinsic Stability of Liposomes

Abstract

Though the aggregation of glycosaminoglycans (GAGs) in the presence of liposomes and divalent cations has been previously reported, the effect of different GAG species, as well as minor changes in GAG composition on the aggregates formed is yet unknown. If minor changes in GAG composition produce observable changes in liposome aggregate diameter or zeta potential, such a phenomenon may be used to detect potentially dangerous over-sulfated contaminants in heparin. We studied the mechanism of the interactions between heparin and its over-sulfated glycosaminoglycan contaminants with liposomes. Herein, we demonstrate that Mg2+ acts to shield the incoming glycosaminoglycans from the negatively-charged phosphate groups of the phospholipids, and that changes in the aggregate diameter and zeta potential are a function of glycosaminoglycan species and concentration, as well as liposome bilayer composition. These observations are supported by TEM studies. We have shown that organizational states of the liposome bilayers are influenced by the presence of GAG and excess Mg2+, resulting in a stabilizing effect which increases the Tm value of DSPC liposomes; the magnitude of this effect is also dependent on GAG species and concentration present. There is an inverse relationship between the percent change of aggregate diameter and percent change of aggregate zeta potential, as a function of GAG concentration in solution. Finally, we demonstrate that the diameter and zeta potential changes of POPC liposome aggregates in the presence of different over-sulfated heparin contaminants at low concentrations allow accurate detection of over-sulfated chondroitin sulfate at concentrations as low as 1 mol%.

Controlled Release of Nitric Oxide from Liposomes

“…Liposomes made from DMPC (C 14 ) and DPPC (C 16 ) remained similar in size (∼200 nm) with comparable PDI and EE values (∼30%). In contrast, liposomes prepared using DSPC (C 18 ) were significantly larger (340 nm) and more polydisperse, likely due to the longer alkyl chains disrupting bilayer formation . Anionic DPPG liposomes exhibited size and monodispersity similar to those of neutral DPPC liposomes (Table and Figure S9) but demonstrated an 11% decrease in EE.…”

Tuning the Extent and Depth of Penetration of Flexible Liposomes in Human Skin

“…Heparins were chosen since glycosaminoglycans exhibit a high affinity for cationic lipids and therefore can severely influence the physicochemical features of liposomes in terms of ζ-potential, aggregation state, and stability. , It is then expected that the complexation between drug and lipid components would affect the ability of the lipid bilayer to rearrange its structure, thus altering its elastic properties. Moreover, heparins were selected as model compounds since they are not able to cross the skin due to their unfavorable physicochemical properties .…”

N-Doped Yellow-Emissive Carbon Nanodots from Gallic Acid: Reaction Engineering, Stimuli-Responsive Red Emission, and Intracellular Localization

“…To further identify the state of emission upon addition of acid, we have carried out zeta potential studies of the fluorophore in an aqueous medium before and after the addition of acid. Acid addition has forced the zeta potential to lie in a range of agglomeration, −10 to −15 mV (Figure D) . Hence, it suffices to ascertain that a proton has elicited the fluorophore to organize in an aggregated state with strong emissivity.…”

“…Acid addition has forced the zeta potential to lie in a range of agglomeration, −10 to −15 mV (Figure 5D). 55 Hence, it suffices to ascertain that a proton has elicited the fluorophore to organize in an aggregated state with strong emissivity. The origin of red emission may thus be attributed to the strong interactions of πelectrons present in aromatic rings of the fluorophore.…”