Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 93, Issue -, Pages 149-164Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2015.03.024
Keywords
Compound 48/80; Chitosan; Alginate; Nanoparticles; Mast cell activator; Nasal vaccination; Mucosal immunity; Anthrax protective antigen
Categories
Funding
- FEDER European funds through the Programa Operacional Factores de Competitividade - COMPETE
- Portuguese funds through FCT - Portuguese Foundation for Science and Technology [PTDC/SAU-FAR/115044/2009, PEst-C/SAU/LA0001/2013-2014]
- FCT doctoral fellowship [SFRH/BD/65141/2009]
- FCT [REEQ/1062/CTM/2005, REDE/1512/RME/2005]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/65141/2009, PTDC/SAU-FAR/115044/2009] Funding Source: FCT
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In a time in which mucosal vaccines development has been delayed by the lack of safe and effective mucosal adjuvants, the combination of adjuvants has started to be explored as a strategy to obtain potent vaccine formulations. This study describes a novel adjuvant combination as an effective approach for a nasal vaccine the association of the mast cell activator compound 48/80 with chitosan based nanopartides. It was hypothesized that mucoadhesive nanoparticles would promote the cellular uptake and prolong the antigen residence time on nasal cavity. Simultaneously, mast cell activation would promote a local microenvironment favorable to the development of an immune response. To test this hypothesis, two different C48/80 loaded nanoparticles (NPs) were prepared: Chitosan-C48/80 NP (Chi-C48/80 NP) and Chitosan/Alginate-C48/80 NP (Chi/Alg-C48/80 NP). The potential as a vaccine adjuvant of the two delivery systems was evaluated and directly compared. Both formulations had a mean size near 500 nm and a positive charge; however, Chi-C48/80 NP was a more effective adjuvant delivery system when compared with Chi/Alg-C48/80 NP or C48/80 alone. Chi-C48/80 NP activated mast cells at a greater extent, were better internalized by antigen presenting cells than Chi/Alg-C48/80 NP and successfully enhanced the nasal residence time of a model antigen. Superiority of Chi-C48/80 NP as adjuvant was also observed in vivo. Therefore, nasal immunization of mice with Bacillus anthracis protective' antigen (PA) adsorbed on Chi-C48/80 NP elicited high levels of serum anti-PA neutralizing antibodies and a more balanced Th1/Th2 profile than C48/80 in solution or Chi/Alg-C48/80 NP. The incorporation of C48/80 within Chi NP also promoted a mucosal immunity greater than all the other adjuvanted groups tested, showing that the combination of a mast cell activator and chitosan NP could be a promising strategy for nasal immunization. (C) 2015 Elsevier B.V. All rights reserved.
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