Polymeric Nanogels Produced via Inverse Microemulsion Polymerization as Potential Gene and Antisense Delivery Agents

• Published in: Journal of the American Chemical Society Vol. 124; no. 51; pp. 15198 - 15207
• Main Authors: McAllister, Karen, Sazani, Peter, Adam, Mirielle, Cho, Moo J, Rubinstein, Michael, Samulski, Richard Jude, DeSimone, Joseph M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 25.12.2002
• Subjects: Acrylates - chemistry; Biological and medical sciences; Chromatography, Gel; DNA - administration & dosage; DNA - chemistry; DNA - pharmacokinetics; DNA, Antisense - administration & dosage; DNA, Antisense - chemistry; DNA, Antisense - pharmacokinetics; Drug Stability; Electrophoresis; Emulsions; Fundamental and applied biological sciences. Psychology; Gels - chemical synthesis; Gels - chemistry; Gels - pharmacokinetics; Gels - toxicity; Gene Transfer Techniques; Genetic Vectors - chemical synthesis; Genetic Vectors - chemistry; Genetic Vectors - pharmacokinetics; Genetic Vectors - toxicity; HeLa Cells; Humans; Light; Microscopy, Confocal; Microscopy, Electron; Molecular and cellular biology; Nanotechnology - methods; Oligonucleotides - administration & dosage; Oligonucleotides - chemistry; Oligonucleotides - pharmacokinetics; Polyethylene Glycols - chemistry; Polymers - chemical synthesis; Polymers - chemistry; Polymers - pharmacokinetics; Polymers - toxicity; Scattering, Radiation; Genetics
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja027759q

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.