Abstract

Nanoparticles prepared from natural or synthetic polymers have shown potential for antigen and DNA vaccine delivery to mucosal surfaces. The purpose of this research was to prepare chitosan/poly-e-caprolactone (Chitosan/ PCL) nanoparticles and PCL nanoparticles and evaluate their potential as DNA and protein/vaccine delivery systems. Both preparation methods resulted in particles of low cytotoxicity and sizes suggested to be ideal to be taken up by cells (199 ± 62 nm and 165 ± 35 nm, respectively for chitosan/PCL and PCL nanoparticles). However, Chitosan/ PCL nanoparticles offered considerable advantages over PCL nanoparticles as antigen and DNA delivery system. Namely, higher loading efficacies for model antigens studied (myoglobin, BSA, ovalbumin, lactalbumin, α-casein and lysozyme), much higher uptake by A549 cells, great ability to form stable complexes, which protect DNA from nucleases. However, in spite of good DNA and protein loading capabilities, Chitosan/PCL nanoparticles showed much better qualities as a protein delivery system since the rate of cells transfected were not very high.

Highlights

  • In developing countries traditional vaccines are mostly administered by injection, which potentially results in a significant transmission of viral infections, due to the reuse of material and unsafe injection practices

  • The chitosan purification process did not induce any modification in the acetylation degree as confirmed by Fourier Transform Infrared Spectroscopy (FTIR).The precipitation technique allowed us to efficiently produce two different types of nanoparticles: Chitosan/PCL nanoparticles and PCL nanoparticles

  • Chitosan/PCL nanoparticles presented advantages over PCL nanoparticles in terms of protein loading and pDNA complexation. These particles were shown to be stable in a freeze-dried formulation, suitable for antigen loading, antigen transport and delivery to epithelial cells in vitro

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Summary

Introduction

In developing countries traditional vaccines are mostly administered by injection, which potentially results in a significant transmission of viral infections, due to the reuse of material and unsafe injection practices. When a vaccine is administered mucosally it encounters the same host defense barriers as do microbial pathogens and other foreign macromolecules They are diluted in mucosal secretions, retained and cleared in mucus gels, attacked by proteases and nucleases and barred by the epithelial barrier, which leads to a poor and limited contact of the formulations with the nasal mucosal epithelium itself [2,3]. Even so, this region presents advantages that are worth exploiting for nasal immunization, for instance the high amount of lymphoid tissue in the nasal passages and the potential eliciting of both mucosal and systemic immune responses [2]

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