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Formulation of a microparticle carrier for oral polyplex-based DNA vaccines
Kenneth A Howard1, Xiong Wei Li, Satyanarayana Somavarapu
1Centre for Drug Delivery Research, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Biochimica Et Biophysica Acta
|September 18, 2004
Summary
Developing microparticle carriers for oral DNA vaccines ensures intact polyplexes reach the gut's immune tissues. This study shows these carriers enable gene expression in spleen tissue after oral administration, paving the way for effective mucosal vaccination.
Area of Science:
- Biotechnology
- Vaccine Development
- Nanotechnology
Background:
- Oral mucosal vaccines require intact polyplexes delivered to gastrointestinal lymphoid tissues.
- Current methods face challenges in delivering these complexes effectively.
Purpose of the Study:
- To formulate and evaluate microparticle carriers for oral delivery of polyplex-based DNA vaccines.
- To demonstrate the successful encapsulation, release, and in vivo transfection of polyplexes using these carriers.
Main Methods:
- Formulation of PEGylated PEI/DNA polyplexes and their encapsulation into PLGA microparticles using a double emulsion solvent evaporation method.
- Assessment of polyplex stability, encapsulation efficiency, and release kinetics.
- In vivo oral administration of microparticles to Wistar rats and analysis of transgene expression in spleen tissue.
Main Results:
- Stable, concentrated PEGylated polyplexes were formulated with maintained luciferase gene expression.
- PLGA microparticles achieved approximately 17% DNA encapsulation efficiency.
- Oral administration of microparticles resulted in significant transgene expression in the spleen 72 hours post-administration.
Conclusions:
- Microparticle carriers can successfully protect and deliver intact polyplexes for oral mucosal vaccination.
- This approach shows potential for enhancing the efficacy of DNA vaccines administered orally.
- Further research can optimize this system for widespread application in vaccine development.
