• Medientyp: E-Artikel
  • Titel: Cationic Graft Copolymers as Carriers for Delivery of Antisense‐Oligonucleotides
  • Beteiligte: Dautzenberg, Herbert; Koňák, Čestmír; Reschel, Tomáš; Zintchenko, Arkadi; Ulbrich, Karel
  • Erschienen: Wiley, 2003
  • Erschienen in: Macromolecular Bioscience
  • Sprache: Englisch
  • DOI: 10.1002/mabi.200350014
  • ISSN: 1616-5187; 1616-5195
  • Schlagwörter: Materials Chemistry ; Polymers and Plastics ; Biomaterials ; Bioengineering ; Biotechnology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Self‐assembling systems based on ionic complexes of DNA fragments (36 base pairs), bcl‐2 antisense oligonucleotides (octadecamer), oligophosphates (25 phosphate groups) or acrylic oligomers (18 groups of phosphonic acid) with poly(<jats:sc>L</jats:sc>‐lysine) (PLL) (<jats:styled-content>$\overline M _{\rm w}$<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-ueqn-1.gif" xlink:title="equation image" /></jats:styled-content> = 130 000 and 88 000) grafted with short poly[<jats:italic>N</jats:italic>‐(2‐hydroxypropyl)methacrylamide] (PHPMA) chains (<jats:styled-content>$\overline M _{\rm n}$<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-ueqn-2.gif" xlink:title="equation image" /></jats:styled-content> = 4 300 or 8 600) were studied by static and dynamic light scattering methods as systems suitable for gene therapy applications. The graft copolymers (GPLLs) with shorter PHPMA grafts (<jats:styled-content>$\overline M _{\rm n}$<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-ueqn-3.gif" xlink:title="equation image" /></jats:styled-content> = 4 300) provide polyelectrolyte complexes (PECs) with smaller<jats:styled-content>$\overline M _{\rm w}$<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-ueqn-4.gif" xlink:title="equation image" /></jats:styled-content>and<jats:italic>R</jats:italic><jats:sub>H</jats:sub>than the corresponding GPLLs with longer grafts (<jats:styled-content>$\overline M _{\rm n}$<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-ueqn-5.gif" xlink:title="equation image" /></jats:styled-content> = 8 600) and the same content of PLL. The lowest aggregation number of 2 was observed for PECs prepared from the GPLL with short grafts and 40 wt.‐% of PLL. The complexes of oligonucleotides and DNA fragments with GPLLs showed quite similar behavior to that with oligophosphates and acrylic oligomer. The complexes prepared from GPLLs containing 40 wt.‐% of PLL and at excess of oligophosphate were stable for at least 48 h under physiological conditions (0.15<jats:sc>M</jats:sc>NaCl) and in bovine serum albumin solutions (1 mg · mL<jats:sup>−1</jats:sup>). Additionally, polyanion exchange reactions of the PECs in contact with poly(styrenesulfonate) and DNA were studied in 0.15<jats:sc>M</jats:sc>NaCl solutions. The oligophosphates in complexes were at least partially substituted with high‐molecular‐weight polyanions. The structure of the initial PECs dominated the PEC structure after the exchange reaction.</jats:p><jats:p><jats:boxed-text content-type="graphic" position="anchor"><jats:caption><jats:p>The dependence of the molecular weight<jats:styled-content>$\overline M _{\rm w}$<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-ueqn-6.gif" xlink:title="equation image" /></jats:styled-content>(a) and the hydrodynamic radius<jats:italic>R</jats:italic><jats:sub>H</jats:sub>(b) of complexes of the oligophosphate (OPP) and four graft copolymers (GPLLi,<jats:italic>i</jats:italic> = 0–3) on the mixing ratio<jats:italic>X</jats:italic>.</jats:p></jats:caption><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/gif" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/mgra001.gif"><jats:alt-text>magnified image</jats:alt-text><jats:caption><jats:p>The dependence of the molecular weight<jats:styled-content>$\overline M _{\rm w}$<jats:inline-graphic xlink:href="graphic/tex2gif-ueqn-6.gif" xlink:title="equation image" /></jats:styled-content>(a) and the hydrodynamic radius<jats:italic>R</jats:italic><jats:sub>H</jats:sub>(b) of complexes of the oligophosphate (OPP) and four graft copolymers (GPLLi,<jats:italic>i</jats:italic> = 0–3) on the mixing ratio<jats:italic>X</jats:italic>.</jats:p></jats:caption></jats:graphic></jats:boxed-text></jats:p>