Biomedical subjects

Gleb Sukhorukov

Publications and source records attributed to Gleb Sukhorukov.

3 recordsLinked to original sources

PubMed2004

Polyelectrolyte nanoparticles mediate vascular gene delivery.

PURPOSE: The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. METHODS: We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. RESULTS: We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. CONCLUSIONS: A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.

Animals↗

PubMed2002

A novel method for encapsulation of poorly water-soluble drugs: precipitation in polyelectrolyte multilayer shells.

A novel method to include poorly water-soluble substances into the polyelectrolyte capsules of defined size, stability, composition and affinity properties is proposed. Encapsulation explores the polarity gradient across the capsule wall. Capsules creation makes use of electrostatic interaction and can involve many substances as layer constituents, such as synthetic polyelectrolytes, proteins, nucleic acids, lipids and multivalent dyes. Using capsules made of synthetic polyelectrolytes as a model system was demonstrated how to prepare, to measure and to use this gradient for low molecular weigh materials encapsulation.

Capsules↗

PubMed2002

Characterization of structure and mechanism of transfection-active peptide-DNA complexes.

We studied a number of physicochemical parameters of transfection-active peptide-DNA complexes including size, aggregation behaviour and circular dichroism (CD) spectra. These data were brought in relationship to the transfection activity of these peptides in order to better understand the mechanism of peptide-mediated gene transfer. A DNA binding oligolysine (K(16)) and a peptide comprising K(16) with an added peptide loop containing the arbitrary sequence RAD not known as a receptor ligand were used. Whereas the K(16)-DNA complex at 88% charge neutralization of the DNA phosphates collapsed into small toroidal particles with a diameter of 200 nm by dynamic light scattering, K(16)-cRAD did not. Instead, large aggregates were observed. CD spectra showed that the K(16)-DNA complexes were in a -psi state observed at liquid crystalline phases. Increasing positive charge by addition of further K(16) or disturbing the -psi state by introducing the RAD-peptide loop resulted in increasing instability indicated by aggregation and loss of the -psi CD spectrum of the complexes. Transfection experiments indicated that the aggregated material was the transfection-active component.

Cell Line↗