title: Stability of dendriplexes formed by anti-HIV genetic material and poly(propylene imine) dendrimers in the presence of glucosaminoglycans.
abstract: There are several barriers to the application of dendriplexes formed by poly(propylene imine) dendrimers and genetic material for gene therapy. One limitation is their interaction with extracellular matrix components such as glucosaminoglycans. These can displace the genetic material from the dendriplexes, affecting their transfection activity. In this study, we analyzed the interaction between dendriplexes and the four main glucosaminoglycans (heparin, heparan sulfate, chondroitin sulfate, and hyaluronic acid) by fluorescence polarization and gel electrophoresis. Dendriplexes were formed by combining three anti-HIV antisense oligodeoxynucleotides with three poly(propylene imine) dendrimers of the fourth generation: unmodified and partially modified with maltose and maltotriose (open shell glycodendrimers). The data showed that the effect of glucosaminoglycans on dendriplexes depends on the glucosaminoglycan type and the oligosaccharide serving as the surface group of the dendrimer. Heparin at physiological concentrations destroys dendriplexes formed by open shell glycodendrimers, but dendriplexes based on unmodified poly(propylene imine) dendrimers are stable in its presence. The other glucosaminoglycans at physiological concentrations cannot destroy dendriplexes formed by any of the dendrimers studied.
authors.affiliation: Department of General Biophysics, University of Lodz, Pomorska 141/143, 90-237 Lodz, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Szewczyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Drzewinska
authors.forename: Volha
authors.initials: V
authors.lastname: Dzmitruk
authors.forename: Dzmitry
authors.initials: D
authors.lastname: Shcharbin
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
mesh_terms: D001483:Base Sequence; D050091:Dendrimers / Q000737:chemistry*; D004355:Drug Stability; D004586:Electrophoresis; D005454:Fluorescence Polarization; D015316:Genetic Therapy; D006025:Glycosaminoglycans / Q000737:chemistry*; D015497:HIV-1 / Q000235:genetics*; D008958:Models, Molecular; D008968:Molecular Conformation; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics; D010316:Particle Size; D011126:Polypropylenes / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D006025:Glycosaminoglycans; D016376:Oligonucleotides, Antisense; D011126:Polypropylenes; C020341:glucosaminoglycans; C443641:poly(propyleneimine)