Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block.
Self-assembling systems based on ionic complexes of DNA with block copolymer of N-(2-hydroxypropyl)methacrylamide with 2-(trimethylammonio)ethyl methacrylate were studied as systems suitable for gene delivery. In this study, the influence of albumin and polyanion on parameters of the DNA polyelectrolyte complexes in aqueous solutions was investigated. Static and dynamic light-scattering methods were used as a main tool for characterizing these interactions. It was found that albumin is not able to release free DNA, but it can rather bind to the complexes forming ternary DNA-polycation-albumin complexes with increased hydrodynamic radii of about 10 nm. Polyanion tested, sodium poly(styrenesulfonate), was able to release free DNA in the presence of a low-molecular-weight electrolyte. In the absence of a low-molecular-weight electrolyte, only formation of ternary complexes and no DNA release was observed. The in vivo biodistribution analysis of DNA complexes showed no effect of the presence of hydrophilic nonionic poly(HPMA) on the circulatory time or organ distribution. The interaction of DNA complexes with albumin and other plasma proteins was suggested to be a major reason for the short circulatory times.
Oupický
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Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic. oupicky@imc.cas.cz
Konák
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Dash
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Seymour
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Ulbrich
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D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000493:pharmacokinetics; D004587:Electrophoresis, Agar Gel; D008027:Light; D008689:Methacrylates / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009690:Nucleic Acid Conformation; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D004247:DNA; D008689:Methacrylates; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers; D012710:Serum Albumin, Bovine; C120889:2-(trimethylammonio)ethyl methacrylate; C032802:hydroxypropyl methacrylate