pH-Dependent Aggregation Properties of Mixtures of Sugar-Based Gemini Surfactants with Phospholipids and Single-Tailed Surfactants

Abstract

Sugar-based gemini surfactants (GSs) display rich pH-dependent phase diagrams and are considered to be promising candidates as gene- and drug-delivery vehicles for biomedical applications. Several sugar-based GSs form vesicles around neutral pH. The vesicular dispersions undergo transitions toward wormlike micelles and spherical micelles at acidic pH, whereas flocculation followed by redispersion upon charge reversal is observed at basic pH. The influence of various amounts of the double-tailed phospholipids DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) and DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and of the single-tailed surfactants lyso-PC (1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine) and OTAC (octadecyltrimethylammonium chloride) on the phase behavior of GS1 (1,8-bis(N-octadec-9-yl-1-deoxy-D-glucitol-1-ylamino)3,6-dioxaoctane) was determined as a function of pH, in water and in water at physiological ionic strength. The pH corresponding to the phase transitions and the characteristics of the aggregates were determined by means of a combination of physical techniques: static and dynamic light scattering (SLS and DLS), fluorescence spectroscopy, cryo-TEM and diffusion- and (31)P NMR. The results show that the additives affect the phase behavior of the GS1 dispersions in a pH-dependent fashion. In the presence of double-tailed phospholipids, a higher degree of protonation of GS1 must be reached to observe micelle formation, whereas single-tailed surfactants affect these transitions only slightly. In the presence of increasing amounts of lyso-PC, the pH range of flocculation becomes more narrow, indicating the increased hydration of the vesicles. The pH of redispersion after charge reversal is particularly sensitive to the presence of positively charged additives. It is suggested that the cationic headgroups disturb the hydrogen-bond structure of water at the vesicular surface, hampering OH(-) binding. The effect of an increase in ionic strength to physiological values is found to be modest, except for the dispersions containing the positively charged additives.

Transfection mediated by pH-sensitive sugar-based gemini surfactants; potential for in vivo gene therapy applications

“…In this context, it is relevant to note that in very recent work, applying a novel and highly sensitive assay to monitor lipid phase changes [46], we have determined that upon acidification, GS1 and GS2 lipoplexes undergo a lamellar to a H I non-inverted micellar transition and that this transition is impeded when the H II (i.e., inverted) phase preferring DOPE is included [33] (Wasungu et al, submitted for publication). These data, thus, entirely explain the observation that DOPE inhibits rather than promotes transfection of gemini complexes.…”

“…Such gemini surfactants [30] do not require helper lipids, as is the case for numerous cationic lipid-based systems, and, most importantly, liposomes prepared from such surfactants show a pH-dependent transition from the lamellar to a micellar phase [30][31][32]. In fact, helper lipids, like DOPE, frustrate this transition, thus causing a relative stabilization of the bilayer structure and emphasizing the membrane destabilizing micellar phase as a prerequisite for cytoplasmic DNA release [33]. The potential of the gemini surfactant systems for gene delivery in vitro has been demonstrated [34,35].…”

Wormlike Micelles in Mixed Amino Acid‐Based Anionic Surfactant and Zwitterionic Surfactant Systems

“…The formation of wormlike micelles is very sensitive to many factors, such as pH [17][18][19], surfactant structure [20], counter-ion [21][22][23][24][25], temperature [26], and even light [27,28]. Wormlike micelles of cationic surfactants formed with salts were widely studied in past years [29,30].…”

Investigation of binary polymer/surfactant or ternary polymer/surfactant/Cu2+ complexes in aqueous solution through Nile red probing

“…Because of these properties, Nile red is widely used as a staining agent in biology,15 in the investigation of disperse systems, like microemulsions16, 17 or other polymeric colloids,18, 19 as well as a guest for studying host–guest systems 20–22. While Nile red has been used for the characterization of surfactants23–28 and polymer/surfactant interactions,18 it has not been systematically exploited for the determination of CAC or CMC 18, 26…”