Olga V. Zaborova

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.

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.

Interaction of copolymers of dimethylsiloxane and ethylene oxide with model membranes and cancerous cells

Interaction of amphiphilic copolymers and ethylene oxide and dimethylsiloxane with biological membranes is studied. Copolymers are shown to increase the permeability of model membranes. Has been shown that their effect on the permeability of liposomal membranes with respect to dye carboxyfluoresceine correlates with their toxicity. At low nontoxic concentrations, Pluronic L61, a diblock copolymer of dimeth-ylsiloxane and ethylene oxide similar to triblock copolymer of ethylene and propylene oxides, is able to reduce the concentration of chemotherapeutic drug doxorubicin by a factor of 30, which is toxic to cancerous cells stable to remedy drugs.

Structure and properties of complexes of polycationic brushes with anionic liposomes

The adsorption of anionic lipid vesicles (liposomes) on the surfaces of colloidal particles containing grafted polycationic chains (cationic brushes) is studied. The stability of liposome-brush complexes in aqueous salt solutions increases with the content of anionic lipid in the liposomal membrane; complexes with liposomes containing 20 and 30 mol% anionic lipids do not dissociate into individual components in a 1.2 M NaCl solution. The integrity of the brush-bound liposomes is preserved. The developed approach can be used to obtain nanosized carriers for biologically active compounds.

Electrostatic complexes of liquid and solid liposomes with spherical polycationic brushes

The complexation of anionic liposomes and polymeric microspheres with grafted polycationic chains (spherical polycationic brushes) is studied. Three types of liposomes with the same molar amount of the anionic lipid are used, namely, liquid liposomes with a high mobility of lipids within the bilayer, solid liposomes with limited lateral and transmembrane mobility of lipid molecules, and solid liposomes with embedded cholesterol. All liposomes efficiently adsorb on the surface of brushes. Upon adsorption, solid liposomes begin to “leak,” that is, to release water-soluble contents in the surrounding solution, whereas solid liposomes with the embedded cholesterol preserve their integrity. Cholesterol-containing liposomes are of interest for obtaining multiliposomal containers with encapsulated biologically active compounds, catalysts, diagnostic agents, etc.

Competitive Reactions in Three-Component System Cationic Colloid–Anionic Liposome–Protein

The formation of complexes of anionic liposomes (50 nm) and polymer microspheres with grafted polycationic chains with a diameter of 240 nm (spherical polycationic brushes) in a physiological solution at a NaCl concentration of 0.15 mol/L is investigated. Liposomes are quantitatively adsorbed on the surface of brushes; every brush can bind up to 24 intact liposomes. The saturated brush–liposome complex is able to additionally bind negatively charged protein albumin; the excess of protein does not displace liposomes from the complex with brushes. The obtained results are important for understanding the mechanism of formation and functioning of electrostatic multiliposomal containers in biological media containing a high amount of protein.