Development of a formulation platform for a spray-dried, inhalable tuberculosis vaccine candidate
| Autor: | Isobel Tetreau, Mani Ordoubadi, Alana Gerhardt, Joseph McCollum, Michelle Archer, Nicholas B. Carrigy, Reinhard Vehring, Ryan M. Kramer, Christopher B. Fox, Chris Press, Mellissa Gomez, Chester Jar, Hui Wang, David Barona |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Pharmaceutical Science Excipient 02 engineering and technology 030226 pharmacology & pharmacy Article Excipients 03 medical and health sciences chemistry.chemical_compound Squalene 0302 clinical medicine Adjuvants Immunologic Administration Inhalation medicine Humans Tuberculosis Particle Size Tuberculosis Vaccines Aerosols Chromatography Pullulan 021001 nanoscience & nanotechnology Trehalose chemistry Spray drying Emulsion Powders 0210 nano-technology Tuberculosis vaccines Adjuvant medicine.drug |
| Zdroj: | Int J Pharm |
| ISSN: | 1873-3476 |
| Popis: | Protection against primarily respiratory infectious diseases, such as tuberculosis (TB), can likely be enhanced through mucosal immunization induced by direct delivery of vaccines to the nose or lungs. A thermostable inhalable dry powder vaccine offers further advantages, such as independence from the cold chain. In this study, we investigate the formulation for a stable, inhalable dry powder version of ID93 + GLA-SE, an adjuvanted subunit TB vaccine candidate, containing recombinant fusion protein ID93 and glucopyranosyl lipid A (GLA) in a squalene emulsion (SE) as an adjuvant system, via spray drying. The addition of leucine (20% w/w), pullulan (10%, 20% w/w), and trileucine (3%, 6% w/w) as dispersibility enhancers was investigated with trehalose as a stabilizing agent. Particle morphology and solid state, nanoemulsion droplet size, squalene and GLA content, ID93 presence, and aerosol performance were assessed for each formulation. The results showed that the addition of leucine improved aerosol performance, but increased aggregation of the emulsion droplets was demonstrated on reconstitution. Addition of pullulan preserved emulsion droplet size; however, the antigen could not be detected after reconstitution. The trehalose-trileucine excipient formulations successfully stabilized the adjuvant system, with evidence indicating retention of the antigen, in an inhalable dry powder format suitable for lung delivery. |
| Databáze: | OpenAIRE |
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