Cross-Linked Microparticles as Carriers for the Delivery of Plasmid DNA for Vaccine Development
- 28 April 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 15 (3) , 467-474
- https://doi.org/10.1021/bc034159n
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.Keywords
This publication has 27 references indexed in Scilit:
- Parallel Synthesis and Biophysical Characterization of a Degradable Polymer Library for Gene DeliveryJournal of the American Chemical Society, 2003
- Long-Term Release and Improved Intracellular Penetration of Oligonucleotide−Polyethylenimine Complexes Entrapped in Biodegradable MicrospheresBiomacromolecules, 2003
- In Vitro and In Vivo Gene Transfer by an Optimized α-Cyclodextrin Conjugate with Polyamidoamine DendrimerBioconjugate Chemistry, 2003
- Low-pH-Sensitive PEG-Stabilized Plasmid−Lipid Nanoparticles: Preparation and CharacterizationBioconjugate Chemistry, 2003
- Gantrez® AN as a new polymer for the preparation of ligand–nanoparticle conjugatesJournal of Controlled Release, 2002
- Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartmentsEuropean Journal of Immunology, 2002
- Antitumor Mechanisms of Oligodeoxynucleotides with CpG and PolyG Motifs in Murine Prostate Cancer Cells: Decrease of NF-κB and AP-1 Binding Activities and Induction of ApoptosisAntisense and Nucleic Acid Drug Development, 2002
- Control of a Mucosal Challenge and Prevention of AIDS by a Multiprotein DNA/MVA VaccineScience, 2001
- PLGA microspheres containing plasmid DNA: Preservation of supercoiled DNA via cryopreparation and carbohydrate stabilizationJournal of Pharmaceutical Sciences, 1999
- Transcription of DNA injected into Xenopus oocytes is influenced by template topologyNature, 1983