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J Control Release. 2013 Dec 28;172(3):773-81. doi: 10.1016/j.jconrel.2013.09.012. Epub 2013 Sep 25.

Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: a needle-free vaccination strategy.

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1
Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15705 Campus Vida, Santiago de Compostela, Spain.

Abstract

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-α). 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.

KEYWORDS:

Co-delivery; Hepatitis B; Imiquimod; Mucosal vaccination; Nanocapsules

PMID:
24076340
DOI:
10.1016/j.jconrel.2013.09.012
[Indexed for MEDLINE]
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