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Aerosolized non-viral nucleic acid delivery in the vaginal tract of pigs

(2016) PHARMACEUTICAL RESEARCH. 33(2). p.384-394
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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.
Keywords
vaginal administration, non-viral gene delivery complexes, aerosolization, mRNA, plasmid DNA, CHLAMYDIA-TRACHOMATIS INFECTION, MESSENGER-RNA, IMMUNE-RESPONSES, GENITAL-TRACT, CANCER-IMMUNOTHERAPY, DENDRITIC CELLS, VACCINES, DNA, MICROINJECTION, TRANSFECTION

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Chicago
Remaut, Katrien, Evelien De Clercq, Oliwia Andries, Koen Rombouts, Matthias Van Gils, LAETITIA CICCHELERO, Ian Vandenbussche, et al. 2016. “Aerosolized Non-viral Nucleic Acid Delivery in the Vaginal Tract of Pigs.” Pharmaceutical Research 33 (2): 384–394.
APA
Remaut, Katrien, De Clercq, E., Andries, O., Rombouts, K., Van Gils, M., CICCHELERO, L., Vandenbussche, I., et al. (2016). Aerosolized non-viral nucleic acid delivery in the vaginal tract of pigs. PHARMACEUTICAL RESEARCH, 33(2), 384–394.
Vancouver
1.
Remaut K, De Clercq E, Andries O, Rombouts K, Van Gils M, CICCHELERO L, et al. Aerosolized non-viral nucleic acid delivery in the vaginal tract of pigs. PHARMACEUTICAL RESEARCH. 2016;33(2):384–94.
MLA
Remaut, Katrien, Evelien De Clercq, Oliwia Andries, et al. “Aerosolized Non-viral Nucleic Acid Delivery in the Vaginal Tract of Pigs.” PHARMACEUTICAL RESEARCH 33.2 (2016): 384–394. Print.
@article{7097645,
  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.},
  author       = {Remaut, Katrien and De Clercq, Evelien and Andries, Oliwia and Rombouts, Koen and Van Gils, Matthias and Cicchelero E, Laetitia and Vandenbussche, Ian and Van Praet, Sarah and Manuel Benito, Juan and Garcia Fernand{\'e}z, Jos{\'e} Manuel and Sanders, Niek and Vanrompay, Daisy},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keyword      = {vaginal administration,non-viral gene delivery complexes,aerosolization,mRNA,plasmid DNA,CHLAMYDIA-TRACHOMATIS INFECTION,MESSENGER-RNA,IMMUNE-RESPONSES,GENITAL-TRACT,CANCER-IMMUNOTHERAPY,DENDRITIC CELLS,VACCINES,DNA,MICROINJECTION,TRANSFECTION},
  language     = {eng},
  number       = {2},
  pages        = {384--394},
  title        = {Aerosolized non-viral nucleic acid delivery in the vaginal tract of pigs},
  url          = {http://dx.doi.org/10.1007/s11095-015-1796-x},
  volume       = {33},
  year         = {2016},
}

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