Chitosan nanocarrier systems for delivery of pneumococcal vaccine via nebulization

Nicoletta Zallocco, Eliane N. Miyaji, Viviane M. Goncalves, Douglas B. Figueiredo, Imran Y. Saleem, Ronan MacLoughlin

Background: Streptococcus pneumoniae enters the human body via the lungs and is the main cause of pneumonia. The current vaccine is administered via the parenteral route and has limited protection in the lungs and towards the different strains of S. pneumoniae. Pulmonary vaccination is an attractive alternative targeting dendritic cells (DCs) in the lungs initiating an immune response. To optimise targeting and uptake by DCs, chitosan (CHT) and chitosan hydrochloride (CHCl) nanoparticles (NPs) were loaded with pneumococcal surface protein A (PspA) and delivered via nebulization for pulmonary delivery.
Methods: CHT/PspA and CHCl/PspA NPs were prepared by ionic gelation method. The formulations were then collected by centrifugation (35,000rpm, 10min, 25°C) to remove unbound PspA and re-suspended in 1mL of 0.9% NaCl for nebulization. NPs were characterised in terms of particle size, surface charge, polydispersity index (PDI), drug loading after centrifugation, post nebulization dose, particle morphology, in vitro release and cell viability (DCs) after 24h.
Results: Results indicated the size of CHT/PspA NPs (236.36±5.57nm, +10.78±0.47mV, PDI 0.366±0.045), CHCl/PspA NPs (372.633±7.02nm, +31.8±1.16mV, PDI 0.216±0.025) were suitable for targeting DCs. PspA loading after centrifugation and nebulization (CHT/PspA NPs: 9.92μg/mg,9.69 μg/mg), and (CHCl/PspA NPs: 1.62μg/mg, 1.29 μg/mg) indicated little loss. The release studies revealed continuous release of protein after 24h (CHT/PspA NPs: 26%, CHCl/PspA NPS: 99%). The NPs appear to be well tolerated by DCs.
Conclusion: The results indicated chitosan NPs could be a promising candidate for pulmonary delivery of pneumococcal vaccine.

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