Research Paper

Pharmaceutical Research

, Volume 33, Issue 2, pp 384-394

First online:

Aerosolized Non-viral Nucleic Acid Delivery in the Vaginal Tract of Pigs

  • Katrien RemautAffiliated withLaboratory of General Biochemistry and Physical Pharmacy, Ghent University
  • , Evelien De ClercqAffiliated withLaboratory of Immunology and Animal Biotechnology, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University
  • , Oliwia AndriesAffiliated withLaboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University
  • , Koen RomboutsAffiliated withLaboratory of General Biochemistry and Physical Pharmacy, Ghent University
  • , Matthias Van GilsAffiliated withLaboratory of Immunology and Animal Biotechnology, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University
  • , Laetitia CiccheleroAffiliated withLaboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University
  • , Ian VandenbusscheAffiliated withLaboratory of General Biochemistry and Physical Pharmacy, Ghent University
  • , Sarah Van PraetAffiliated withLaboratory of General Biochemistry and Physical Pharmacy, Ghent University
  • , Juan Manuel BenitoAffiliated withInstitute for Chemical Research, CSIC, University of Sevilla
    • , José Manuel Garcia FernandézAffiliated withInstitute for Chemical Research, CSIC, University of Sevilla
    • , Niek SandersAffiliated withLaboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University 
    • , Daisy VanrompayAffiliated withLaboratory of Immunology and Animal Biotechnology, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent UniversityDepartment of Animal Production, Faculty of Bioscience Engineering, Ghent University Email author  

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Abstract

Purpose

The human pathogen Chlamydia trachomatis is worldwide the leading cause of bacterial sexually transmitted disease. Nasal or vaginal nucleic acid vaccination is a promising strategy for controlling genital Chlamydia trachomatis infections. Since naked nucleic acids are generally not efficiently taken up by cells, they are often complexed with carriers that facilitate their intracellular delivery.

Methods

In the current study, we screened a variety of commonly used non-viral gene delivery carriers for their ability to transfect newborn pig tracheal cells. The effect of aerosolization on the physicochemical properties and transfection efficiency of the complexes was also evaluated in vitro. Subsequently, a pilot experiment was performed in which the selected complexes were aerosolized in the vaginal tract of pigs.

Results

Both mRNA and pDNA containing lipofectamine and ADM70 complexes showed promise for protein expression in vitro, before and after aerosolization. In vivo, only lipofectamine/pDNA complexes resulted in high protein expression levels 24 h following aerosolization. This correlates to the unexpected observation that the presence of vaginal mucus increases the efficiency of lipofectamine/pDNA complexes 3-fold, while the efficiency of lipofectamine/mRNA complexes and ADM70/mRNA and ADM70/pDNA complexes decreased.

Conclusions

As aerosolization was an easy and effective method to deliver complexes to the vaginal tract of pigs, we believe this application technique has future potential for both vaginal and perhaps nasal vaccination using non-viral gene delivery vectors.

Key words

plasmid DNA mRNA aerosolization vaginal administration non-viral gene delivery complexes