Cross-linked microparticles as carriers for the delivery of plasmid DNA for vaccine development.
Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polymerization in an inverse emulsion system. Acrylamide-based microspheres 0.2-1 microm in diameter were prepared using an acid-cleavable difunctional monomer. Retention of the DNA payload at physiological pH with complete release under acidic conditions at lysosomal pH was demonstrated. By trapping the plasmid DNA within the cross-linked microparticle, enzymatic degradation was prevented when exposed to serum nucleases. For vaccine development, these delivery vehicles were also investigated for their ability to generate immune responses when delivered to phagocytic cells of the immune system. Encapsulated plasmid DNA demonstrated immunostimulatory activity in macrophages, leading to cytokine secretion of IL-6 with a response approximately 40-fold higher than that achieved with DNA alone.
Goh
Sarah L
SL
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California-Berkeley, Berkeley, CA 94720-1460, USA.
Murthy
Niren
N
Xu
Mingcheng
M
Fréchet
Jean M J
JM
D000818:Animals; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006863:Hydrogen-Ion Concentration; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D008863:Microspheres; D010957:Plasmids / Q000235:genetics*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019444:Vaccines, DNA / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D003432:Cross-Linking Reagents; D004337:Drug Carriers; D015850:Interleukin-6; D011108:Polymers; D019444:Vaccines, DNA; D004247:DNA