Cross-linked microparticles as carriers for the delivery of plasmid DNA for vaccine development

Sarah L. Goh, Niren Murthy, Mingcheng Xu, Jean M.J. Fréchet

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polymerization in an inverse emulsion system. Acrylamide-based microspheres 0.2-1 μm 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 ∼40-fold higher than that achieved with DNA alone.

Original languageEnglish (US)
Pages (from-to)467-474
Number of pages8
JournalBioconjugate Chemistry
Volume15
Issue number3
DOIs
StatePublished - May 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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