Andrey V. Sybachin

Liposome fusion rates depend upon the conformation of polycation catalysts.

Cryo-TEM and NaCl-leakage experiments demonstrated that the cationic polymer polylysine induces fusion of anionic liposomes but that the cationic polymer poly(N-ethyl-4-vinylpyridinium bromide) (PEVP) does not, although both polymers bind strongly to the liposomes. The difference was traced to the thickness of the coatings at constant charge coverage. Polylysine is believed to form planar β-sheets that are sufficiently thin to allow membrane fusion. In contrast, looping and disorganization among adsorbed PEVP molecules physically prevent fusion. A similar effect is likely to be applicable to important polycation-induced fusion of cell membranes.

Composition and properties of complexes between spherical polycationic brushes and anionic liposomes.

A spherical polycationic brush (SPB) is made by graft-polymerizing a cationic monomer onto the surface of a 100 nm polystyrene bead. It is possible to adsorb anionic liposomes (40-60 nm diameter) onto the SPBs while maintaining the liposome integrity. The liposomes were constructed with phosphatidyl choline (PC) admixed with 0.05-0.4 mol fraction of an dianionic lipid, cardiolipin (CL(2-)). As shown by electrophoretic mobility measurements, SPB-to-liposome complexation leads to a conversion from the initial positive charge of the copolymer to a negative charge. The higher the CL(2-) content of the liposomes, the lower the concentration needed for charge neutralization. Dynamic light scattering (DLS) revealed that multicomplex aggregates are formed with a maximum size at the SPB/liposome charge-equivalence point. Experiments with fluorescent-labeled liposomes show that at low CL(2-) content about 80 liposomes are adsorbed per SPB. As the mole fraction of CL(2-) increases from 0.05 to 0.4, fewer liposomes adsorb owing to electrostatic repulsion among neighboring liposomes. The effect of added NaCl also depends upon the CL(2-) content. With 0.05 mol fraction CL(2-), the SPB/liposome complex dissociates into its components at 0.15 M NaCl. With a mole fraction of >0.1, complexes fail to dissociate even at 1.2 M NaCl. Additional information about the SPB/liposome morphology was obtained from cryo-TEM. For example, cryo-TEM data confirm liposome integrity upon complexation, a behavior that contrasts with the liposome destruction as found with adsorption to many other types of surfaces.

Electrostatically Driven Complexation of Liposomes with a Star-Shaped Polyelectrolyte to Low-Toxicity Multi-Liposomal Assemblies†

Anionic liposomes are electrostatically complexed to a star-shaped cationic polyelectrolyte. Upon complexation, the liposomes retain their integrity and the resulting liposome-star complexes do not dissociate in a physiological solution with 0.15 M NaCl. This provides a multi-liposomal container for possible use as a high-capacity carrier.

Lipid Segregation in Membranes of Anionic Liposomes Adsorbed onto Polycationic Brushes

Two-phased: Complexation of liposomes to spherical polycationic brushes induces lipid segregation in the liposomal membrane. The greater the initial anionic lipid content in the membrane, the more the electroneutral lipid dilutes the induced anionic clusters.

Phase separation in solutions of polyelectrolyte complexes: The decisive effect of a host polyion

Boundaries of the existence of insoluble polyelectrolyte complexes in solutions of nonequimolar mixtures of quaternary polyamines and polycarboxylates of various degrees of polymerization have been determined with turbidimetric titration. It has been shown that in salt-free media the position of critical points expressed as the ratio between the charge numbers of polymer components in a mixture depends on the chemical nature of the host polyelectrolyte (polycation or polyanion) but does not depend on either the nature of the guest polyelectrolyte or the degree of polymerization of mixture components. Upon addition of a low-molecular-mass polyelectrolyte, the heterogeneous region widens. The shorter the host polyelectrolyte relative to the guest polyelectrolyte, the more pronounced this effect. Based on the thermodynamic state of the systems under examination, an explanation of this effect is confirmed by the velocity sedimentation data.

Polymeric stabilizers for protection of soil and ground against wind and water erosion

The article is devoted to the design, development and application of a new generation of binders for various dispersed systems, including soil, ground, sand, waste rock and others. The binders are formed by interaction of oppositely charged polyelectrolytes, both chemically stable and (bio)degradable. The fundamental aspects of interpolyelectrolyte reactions are discussed; the IPC structure and properties of the resulting interpolyelectrolyte complexes (IPCs) allow considering them as unique and universal binders. Numerous results of laboratory experiments and field trials of the IPC formulations are presented. In particular, large-scale tests have been done in the Chernobyl accident zone where the IPC binders were shown to be effective means to suppress water and wind erosion thereby preventing a spread of radioactive particles (radionuclides) from contaminated sites. Ecologically friendly IPC compositions are described, including those based on commercially available polymers; prospects for improving their efficiency and extending the range of their possible use are discussed.

Stability of Anionic Liposome-Cationic Polymer Complexes in Water-Salt Media

Laser microelectrophoresis, dynamic light scattering, and fluorescence and UV spectroscopy are employed to study poly-N-ethyl-4-vinylpyridinium bromide adsorption on the surface of bilayer lipid vesicles (liposomes) formed from mixtures of anionic phosphatidyl serine and electroneutral phosphatidylcholine. It is established that polycation adsorption is accompanied by the neutralization of charges on liposomes and their aggregation. The subsequent addition of a low-molecular-weight salt (NaCl) solution to suspensions of complexes causes them to dissociate into their initial components, while the stability of the complexes with respect to the salt action increases with the fraction of the anionic lipid in the liposome membranes. The data obtained are interpreted from the position of the formation-disintegration of a molecular capacitor, the charge of which is generated by spatially separated anionic lipids located in the bilayer membrane and cationic units of the adsorbed polyamine.

Effect of the phase state of the lipid bilayer on the structure and characteristics of the polycation-(anionic liposome) complex

Interaction of the cationic polymer poly-N-ethyl-4-vinylpyridinium bromide with bilayer vesicles (liposomes) composed of zwitterionic dipalmitoylphosphatidylcholine and anionic cardiolipin (the molar fraction of the negatively charged cardiolipin groups is 0.2) is studied. The composition and characteristics of the polycation-liposome complex are shown to be controlled by the phase state of the lipid membrane. Liposomes whose membranes exist in their LC state (“liquid” liposomes) keep their integrity in the complex with polycation. The adsorbed polycation can be completely removed from the liposomal membrane by the addition excess amounts of a competing polyanion. The adsorption of polycation on the surface of liposomes whose membranes exist the gel state (“solid” liposomes) leads to the formation of defects in the membrane, and the polycation’s adsorption with such liposomes becomes irreversible. The defects that form are also preserved when solid liposomes on whose surface the polycation is sorbed are transformed into the liquid state. Moreover, the reversible contact between polycation and liquid liposomes becomes irreversible once the liposomal membranes bound to the polycation transform into the solid state.

Biodegradable containers composed of anionic liposomes and cationic polypeptide vesicles

An electrostatic complexation of liposomes, composed of anionic palmitoyloleoyl phosphatidylserine (POPS1−) and zwitterionic dioleoylphophatidylcholine (DOPC), with bilayer vesicles composed of cationic poly(L-lysine)-b-poly(L-leucine) block copolypeptides has been investigated. The complexation was characterized by several physicochemical methods with the following main conclusions: (a) all added liposomes are totally adsorbed on the polypeptide vesicles up to a certain saturation concentration. (b) The calculated number of liposomes per a single polypeptide vesicle is about 60. (c) The liposomes remain intact (i.e., do not leak) after being complexed with the vesicles. (d) Complexes are stable in physiological ionic strength solution with [NaCl] = 0.15 M. (e) The vesicles are effectively digested by proteolytic enzyme trypsin even when covered by liposomes. These findings as well as the high potential for loading of anionic liposomes and cationic vesicles with biologically active compounds make these multi-liposomal complexes promising in the drug delivery field.

Biodegradable multi-liposomal containers

The method of preparing biodegradable multi-liposomal containers via modification of anionic liposomes with a cationic polymer and subsequent adsorption of the obtained liposome-polymer cationic complex on the surfaces of negatively charged polylactide micelles with grafted polyoxyethylene chains is described. Liposomes preserve their integrity in a ternary micelle-polycation-liposome complex, a circumstance that allows the complex to be used as a multi-liposomal container for encapsulation of bioactive compounds.