title: Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles.
abstract: 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.
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, USA.
authors.forename: Nitesh K
authors.initials: NK
authors.lastname: Kunda
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Iman M
authors.initials: IM
authors.lastname: Alfagih
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Sao Paulo, SP, Brazil.
authors.forename: Eliane N
authors.initials: EN
authors.lastname: Miyaji
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Sao Paulo, SP, Brazil.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Figueiredo
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Sao Paulo, SP, Brazil.
authors.forename: Viviane M
authors.initials: VM
authors.lastname: Gonçalves
authors.affiliation: Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ferreira
authors.affiliation: UCLan Biomedical Research Facility, Research and Innovation, University of Central Lancashire, Preston, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University College London, London, UK.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hutcheon
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK. Electronic address: i.saleem@ljmu.ac.uk.
authors.forename: Imran Y
authors.initials: IY
authors.lastname: Saleem
mesh_terms: D000280:Administration, Inhalation; D000327:Adsorption; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D007781:Lactoferrin / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D011208:Powders; C051592:pneumococcal surface protein A; D007781:Lactoferrin
keywords: Antigen delivery system; Dendritic cells; Dry powder inhalation; Nanocomposite microcarrier; Nanoparticle; Pneumococcal surface protein A (PspA)