Stability of Dendriplexes Formed by Anti-HIV Genetic Material and Poly(propylene imine) Dendrimers in the Presence of Glucosaminoglycans

• Published in: The journal of physical chemistry. B Vol. 116; no. 50; pp. 14525 - 14532
• Main Authors: Szewczyk, Michal, Drzewinska, Joanna, Dzmitruk, Volha, Shcharbin, Dzmitry, Klajnert, Barbara, Appelhans, Dietmar, Bryszewska, Maria
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.12.2012
• Subjects: Base Sequence; Dendrimers; Dendrimers - chemistry; Displacement; Drug Stability; Electrophoresis; Fluorescence; Fluorescence Polarization; Genetic Therapy; Genetics; Glycosaminoglycans - chemistry; Heparins; HIV-1 - genetics; Human immunodeficiency virus; Imines; Models, Molecular; Molecular Conformation; Oligonucleotides, Antisense - chemistry; Oligonucleotides, Antisense - genetics; Particle Size; Physical chemistry; Polypropylenes - chemistry; Sulfates
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp304449v

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.