Dry powder inhalation of pneumococcal protein-based nanocarrier vaccine

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Imran Saleem

Liverpool John Moores University, UK

: J Pharm Drug Deliv Res

Abstract

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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 aim of this study was to adsorb Pneumococcal Protein (PspA), onto poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, Nano Particles (NPs) to target lung DCs. Further to formulate these NPs into dry powder Nanocomposite Microparticles (NCMPs) suitable for pulmonary vaccine delivery. NPs were prepared using an emulsion solvent evaporation method and PspA was adsorbed onto the surface of NPs (100:20 [NP: PspA]). The NPs were spray-dried in an aqueous suspension of leucine (1:1.5) to produce NCMPs and characterised in terms of particle size, loading, cell viability, protein stability (SDS-PAGE), integrity (Circular Dichroism, CD), antigenicity (ELISA), immunization and aerosolisation studies. The NPs produced were 322.83±4.25 nm in size with PspA loading 19.68±2.74 μg/mg. The NCMPs resulted in a fine particle fraction (FPF%) >75%. The NPs appear to be well tolerated by DCs cell lines ≥90% cell viability at 19.5 μg/mL after 4 h exposure. SDS-PAGE, CD (α-helical decreased <13% vs. standard PspA) and the antigenicity (>95%) confirmed that PspA was stable in both formulations after spray-drying. The cfu in BALF of mice challenged with pneumococcal bacteria was signifcantly less compared to PspA alone in the lungs or via subcutaneous injection. The PspA loaded NPs were incorporated into NCMPs having excellent aerosolisation characteristics while maintaining protein activity. Hence, it may be feasible to use these carriers for pulmonary vaccine delivery.

Biography

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Imran Saleem is a Reader in Nanomedicne at School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, UK. He has been working in and has published numerous papers in the area of Pulmonary Drug Delivery since 2006. His research work aimed at “Developing novel delivery systems for targeting therapeutic agents to their site of action with particular emphasis on lung diseases via dry powder pulmonary delivery”. He has over 10 years of experience in the area of “Nanoparticle formulation and drug delivery systems”, and has published extensively in peer-reviewed journals, conference abstracts and book chapters.

Email: I.Saleem@ljmu.ac.uk