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Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immunocompromised, the very young and the old, and remains one of the leading causes of death. A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in L-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ∼150 nm and achieved ∼20 μg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31±1.32% and MMAD of 1.70±0.03 μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA.

Original publication

DOI

10.1016/j.ijpharm.2015.09.034

Type

Journal article

Journal

Int J Pharm

Publication Date

30/11/2015

Volume

495

Pages

903 - 912

Keywords

Antigen delivery system, Dendritic cells, Dry powder inhalation, Nanocomposite microcarrier, Nanoparticle, Pneumococcal surface protein A (PspA), Administration, Inhalation, Adsorption, Antigens, Bacterial, Bacterial Proteins, Bacterial Vaccines, Cell Survival, Chemistry, Pharmaceutical, Dendritic Cells, Drug Liberation, Drug Stability, Humans, Lactoferrin, Lung, Nanoparticles, Particle Size, Powders