Development of a formulation platform for a spray-dried, inhalable tuberculosis vaccine candidate

[Display omitted] 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 i...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2021-01, Vol.593, p.120121-120121, Article 120121
Main Authors: Gomez, Mellissa, McCollum, Joseph, Wang, Hui, Ordoubadi, Mani, Jar, Chester, Carrigy, Nicholas B., Barona, David, Tetreau, Isobel, Archer, Michelle, Gerhardt, Alana, Press, Chris, Fox, Christopher B., Kramer, Ryan M., Vehring, Reinhard
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Administration, Inhalation
Aerosols
Dispersibility
Excipients
Humans
Inhalable delivery
Nanoencapsulation
Particle engineering
Particle Size
Powders
Spray drying
Tuberculosis
Tuberculosis vaccine
Tuberculosis Vaccines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2020.120121