Imran Saleem
Liverpool John Moores University, UK
Title: Pulmonary delivery of a mucosal nanocarrier vaccine for Pneumonia
Biography
Biography: Imran Saleem
Abstract
Statement of the Problem: There is a huge drive in the vaccine research field, pharmaceutical industry and Bill Gates Foundation for effective targeting of dendritic cells (DCs) to enhance the immune response and for needle-free vaccination. The pulmonary route has an abundance of antigen presenting cells (such as macrophages, DCs) for targeting vaccines. Furthermore, nanoparticles (NPs) due to their size can target DCs enhancing the immune response. However, NPs have poor aerosolization performance as dry powders.
Aim: The aim of this study was to compare encapsulated and adsorbed pneumococcal protein (PspA), onto poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, NPs to target lung DCs. Further to formulate these NPs into dry powder, nanocomposite microparticles (NCMPs) were suitable for pulmonary vaccine delivery.
Methodology & Theoretical Orientation: NPs were prepared using an emulsion solvent evaporation method and PspA was adsorbed (F1) onto the surface of NPs or encapsulated (F2) (100: 20 [NP: PspA]). F1 and F2 were spray-dried in an aqueous suspension of leucine (1:1.5) to produce NCMPs and characterized in terms of particle size, loading, cell viability, protein stability (SDS-PAGE), integrity (circular dichroism, CD), antigenicity (ELISA), aerosolization studies and lung immunization in mice.
Conclusion & Significance: F1 and F2 produced similar size NPs but the PspA loading was significantly greater in F2 (310.4±25.3 nm, 65.73±5.6 µg/mg) compared to F1 (322.83±4.25 nm, 19.68±2.74 µg/mg). F1 had FPF% >75%. The NPs appear to be well tolerated by DCs cell lines (F1 and F2 NPs ≥90% cell viability) at 19.5 µg/mL after 4 h exposure. The antigenicity (>95%) confirmed that PspA was stable in both formulations after spray-drying. F1 induced an earlier control of the infection with lower bacterial load in the lungs after challenge. The results provide an indication that it may be feasible to use these NPs/NCMPs carriers containing protein antigens for pulmonary vaccine delivery against lung infection with pneumococci.
