Journal
MOLECULAR PHARMACEUTICS
Volume 15, Issue 1, Pages 226-237Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00826
Keywords
Newcastle disease; F gene; chitosan derivative nanoparticles; intranasal delivery; mucosal immunity
Funding
- National Key Research and Development Program of China [2017YFD0500706]
- National Natural Science Foundation of China [31570929, 31771000]
- Natural Science Foundation of Heilongjiang Province of China [C2017058]
- Project of Research and Development of Shandong Province of China [2016GSF121020]
- Key Scientific and Technological Planning Project of Harbin [2016AB3BN036]
- Technological innovation talent of special funds for outstanding subject leaders in Harbin [2017RAXXJ001]
- Project of Graduate Innovative Scientific Research Foundation of Heilongjiang University [YjSCX2017-158HLJU]
- Special Project of Graduate Entrepreneurship of Heilongjiang University [20170160907]
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Because mucosal sites are the entry ports of pathogens, immunization via mucosal routes can extremely enhance the immunity. To elevate the potential of N-2-hydroxypropyl trimethylammonium chloride chitosan (N-2-HACC) and N,Ocarboxymethyl chitosan (CMC) nanoparticles as a mucosal immune delivery carrier for DNA vaccines, we prepared the NDV F gene plasmid DNA with C3d6 molecular adjuvant (pVAX I-F(o)-C3d6) encapsulated in the N-2-HACC-CMC nanoparticles (N-2-HACC-CMC/pFDNA-C3d6 NPs). The N-2-HACC-CMC/pFDNA-C3d6 NPs had regular spherical morphology and low toxicity with a mean diameter of 309.7 6.52 nm, zeta potential of 49.9 4.93 mV, encapsulation efficiency of 92.27 1.48%, and loading capacity of 50.75 1.35%. The N-2-HACC-CMC had high stability and safety. The pVAX I-F(o)-C3d6 could be sustainably released from the N-2-HACC-CMC/pFDNA-C3d6 NPs after an initial burst release. Immunization intranasally of chickens with N-2-HACC-CMC/pFDNA-C3d6 NPs not only produced higher anti-NDV IgG and sIgA antibody than chickens in other groups did, but also significantly stimulated lymphocyte proliferation and triggered higher the IL-2, IL-4, and IFN-y levels. These findings indicated that the N-2-HACC-CMC could be used as an efficient delivery carrier for the mucosal immunity of Newcastle disease virus DNA vaccine. The work laid a basis for the quaternized chitosan nanoparticles as efficient mucosal immunity delivery carrier for DNA vaccines and had immense application promise and potential for vaccines and drugs.
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