Journal
JOURNAL OF CONTROLLED RELEASE
Volume 172, Issue 3, Pages 773-781Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2013.09.012
Keywords
Nanocapsules; Hepatitis B; Imiquimod; Co-delivery; Mucosal vaccination
Funding
- Bill & Melinda Gates Foundation
- Spanish Government [CSD2006-00012]
- Xunta de Galicia
- Spanish Institute of Health Carlos III [PI081444]
- Spanish Ministry of Economy and Competitivity [SAF2011-30337-C02-02]
- Spanish Ministry of Education (FPU predoctoral grants program)
- [FP7/REGPOT-2012-2013.1-BIOCAPS-316265]
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Here we report a new nanotechnology-based nasal vaccination concept intended to elicit both, specific humoral and cellular immune responses. The concept relies on the use of a multifunctional antigen nanocarrier consisting of a hydrophobic nanocore, which can allocate lipophilic immunostimulants, and a polymeric corona made of chitosan (CS), intended to associate antigens and facilitate their transport across the nasal mucosa. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the recombinant hepatitis B surface antigen (HB), were selected as model molecules for the validation of the concept. The multifunctional nanocarriers had a nanometric size (around 200 nm), a high positive zeta potential (+45 mV) and a high antigen association efficiency (70%). They also exhibited the ability to enter macrophages in vitro and to effectively deliver the associated imiquimod intracellularly, as noted by the secretion of pro-inflammatory cytokines (i.e. IL-6 and TNF-alpha). However, the nanocarriers did not induce the in vitro activation of the complement cascade. Finally, the positive effect of the co-delivery of HB and imiquimod from the nanocapsules was evidenced upon intranasal administration to mice. The nanocapsules containing imiquimod elicited a protective immune response characterized by increasing IgG levels over time and specific immunological memory. Additionally, the levels of serum IgG subclasses (IgG1 and IgG2a) indicated a balanced cellular/humoral response, thus suggesting the capacity of the nanocapsules to modulate the systemic immune response upon nasal vaccination. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
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