Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Author(s)

Kunda, Nitesh K. ^{[1, 2]} ; Alfagih, Iman M. ^{[1, 3]} ; Miyaji, Eliane N. ^[4] ; Figueiredo, Douglas B. ^[4] ; Goncalves, Viviane M. ^[4] ; Ferreira, Daniela M. ^[5] ; Dennison, Sarah R. ^[6] ; Somavarapu, Satyanarayana ^[7] ; Hutcheon, Gillian A. ^[1] ; Saleem, Imran Y. ^[1]

Affiliation

^[1] Liverpool John Moores Univ, Formulat & Drug Delivery Res, Sch Pharm & Biomol Sci, Liverpool L3 3AF, Merseyside - England

^[2] Univ New Mexico, Coll Pharm, Dept Pharmaceut Sci, Albuquerque, NM 87131 - USA

^[3] King Saud Univ, Coll Pharm, Dept Pharmaceut, Riyadh - Saudi Arabia

^[4] Inst Butantan, Ctr Biotecnol, Sao Paulo, SP - Brazil

^[5] Univ Liverpool, Liverpool Sch Trop Med, Resp Infect Grp, Liverpool L3 5QA, Merseyside - England

^[6] Univ Cent Lancashire, UCLan Biomed Res Facil Res & Innovat, Preston PR1 2HE, Lancs - England

^[7] UCL, Sch Pharm, Dept Pharmaceut, London - England

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 495, n. 2, p. 903-912, NOV 30 2015.
• Web of Science Citations: 14

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 similar to 150 nm and achieved similar to 20 mu g 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 mu m 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. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 15/06255-6 - Development and production of new pneumococcal vaccines based on recombinant proteins
• Grantee: Viviane Maimoni Gonçalves
• Support type: Regular Research Grants
• FAPESP's process: 12/04858-7 - Development of the purification process of the pneumococcal surface protein a from Clade4 (PspA4pro)
• Grantee: Douglas Borges de Figueiredo
• Support type: Scholarships in Brazil - Master