Characterization of complexation of poly (N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate) thermoresponsive cationic nanogels with salmon sperm DNA
Jim Moselhy1, Tasnim Vira1, Fei-Fei Liu2, Xiao Yu Wu1
1Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; 2Ontario Cancer Institute, Toronto, ON, Canada
Abstract: Thermoresponsive cationic nanogel (TCNG) networks based on N-isopropylacrylamide (NIPAM), 2-(dimethylamino)ethyl methacrylate (DMAEMA), and quaternary alkyl ammonium halide salts of DMAEMA (DMAEMAQ) were synthesized by dispersion polymerization technique. The thermoresponsive properties of TCNGs and TCNG-salmon sperm DNA (sasDNA) polyplexes were characterized in aqueous media of various pH and ionic strength. P[NIPAM] and P[NIPAM/DMAEMA] TCNGs exhibited sharp volume phase transition (VPT) in water at critical temperatures (Tc) of 32 °C and 36 °C, respectively. Quaternized P[NIPAM/DMAEMAQ] TCNGs did not undergo sharp VPT up to 50 °C. The VPT of uncomplexed TCNGs were sensitive to the ionic composition and ionic strength of salts in solution, but were insensitive to pH in the range 5.0 to 7.4. The VPT of P[NIPAM/DMAEMAQ]/sasDNA diminished in magnitude with increasing Wp/Wd suggesting greater compaction of the polyplexes. The distinct phase-transition properties of P[NIPAM/DMAEMA]/sasDNA and P[NIPAM/DMAEMAQ]/sasDNA polyplexes were attributed to the condensing capability of polycations and to differences in the spatial distribution of structural charges in quaternized and nonquaternized networks. The findings demonstrate that stable TCNGs can be prepared with controllable responsive properties determined by the nature of the cationic charge incorporated and may have potential as vehicles for DNA delivery.
Keywords: poly(N-isopropyl acryamide), poly(2-dimethylamino)ethyl methacrylate, polyplex, thermoresponsive cationic nanogels
The application of nanotechnology in the field of pharmaceutical formulation development presents exciting opportunities for the discovery of novel medicines and therapeutic regimens that can improve treatment outcomes of many human diseases. Biocompatible nanogels prepared from intelligent polymers that undergo controlled changes in structure and properties in response to a physical or biological stimulus can improve key delivery steps that enhance the efficacy and reduce the toxicity of therapeutic agents. Positively charged chemically crosslinked nanogels prepared from intelligent polymers with temperature- and pH-responsive properties can form stable complexes with DNA. The DNA/nanogel complexes exhibit controllable binding of DNA based on the nature of the cationic charge and regulated response with changes in environmental conditions. Temperature-responsive crosslinked nanogels represent a novel class of DNA carriers that may serve as a platform for delivery of therapeutic genes.
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