Cationic submicron emulsions for pulmonary DNA immunization

• Published in: Journal of controlled release 2004-11, Vol.100 (1), p.145-155
• Main Authors: Bivas-Benita, Maytal, Oudshoorn, Marion, Romeijn, Stefan, van Meijgaarden, Krista, Koerten, Henk, van der Meulen, Hans, Lambert, Gregory, Ottenhoff, Tom, Benita, Simon, Junginger, Hans, Borchard, Gerrit
• Format: Article
• Language: English
• Subjects: Acyltransferases - genetics; Acyltransferases - immunology; Adsorption; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biological and medical sciences; Calu-3 cells; Cationic submicron emulsions; Cell Line; Dendritic cells; Dendritic Cells - physiology; Drug Delivery Systems; Emulsions; General pharmacology; Humans; Immunization; Medical sciences; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pulmonary delivery; Tuberculosis DNA vaccines; Tuberculosis Vaccines - administration & dosage; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2004.08.008

Pulmonary immunization against inhaled pathogens such as Mycobacterium tuberculosis would induce local and systemic immune responses and protect from entry and dissemination of the pathogen. The aim of this study was to evaluate cationic submicron emulsion as a potential carrier for DNA vaccines to the lung. DNA loaded emulsions were 128–152 nm in size and retained positive zeta potential above +40 mV during 3 months of storage. Loading efficiency was above 99%, DNA was protected from DNase I degradation up to 60 min and was stable in presence of 75% fetal calf serum (FCS). The plasmid DNA was detected in the endo-lysosomal compartment of the human bronchial cell line, Calu-3, 6 h after application. No cytotoxic effect on these cells was observed. Human dendritic cells were matured in presence of DNA loaded emulsion, although to a lesser extent than DNA solution indicating slower release and lower exposure to unmethylated CpG sequences. These results indicate that cationic submicron emulsions are potential DNA vaccine carriers to the lung since they are able to transfect pulmonary epithelial cells, which possibly induce cross priming of antigen presenting cells and directly activate dendritic cells, resulting in stimulation of antigen specific T-cells.