Polymeric nanogels produced via inverse microemulsion polymerization as potential gene and antisense delivery agents.
Polymeric nanogel vectors were developed for cellular gene and antisense delivery. Inverse microemulsion polymerization was utilized to synthesize biocompatible nanogels with controlled size, morphology, and composition. The chemical composition, size, polydispersity, stability, and swelling behavior of the nanogels were investigated by NMR, light scattering, transmission electron microscopy, and atomic force microscopy. The cell viability, uptake, and physical stability of nanogel-DNA complexes were evaluated under physiological conditions. Monodisperse nonionic and cationic nanogels were produced with controllable sizes ranging from 40 to 200 nm in diameter. The nanogels demonstrated extended stability in aqueous media and exhibited low toxicity in cell culture. Cationic nanogels formed monodisperse complexes with oligonucleotides and showed enhanced oligonucleotide uptake in cell culture. The nanogels synthesized in this study demonstrate potential utility as carriers of oligonucleotides and DNA for antisense and gene delivery.
McAllister
Karen
K
Department of Chemistry, Campus Box 3290, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Sazani
Peter
P
Adam
Mirielle
M
Cho
Moo J
MJ
Rubinstein
Michael
M
Samulski
Richard Jude
RJ
DeSimone
Joseph M
JM
D000179:Acrylates / Q000737:chemistry; D002850:Chromatography, Gel; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016373:DNA, Antisense / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D004586:Electrophoresis; D004655:Emulsions; D005782:Gels / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D008027:Light; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D036103:Nanotechnology / Q000379:methods; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D012542:Scattering, Radiation
D000179:Acrylates; D016373:DNA, Antisense; D004655:Emulsions; D005782:Gels; D009841:Oligonucleotides; D011108:Polymers; C437167:poly(ethylene glycol)diacrylate; C035957:2-hydroxyethyl acrylate; D011092:Polyethylene Glycols; D004247:DNA