Nasal delivery of Japanese cedar pollen Cryj1 by using self-gelling immunostimulatory DNA for effective induction of immune responses in mice

JOURNAL OF CONTROLLED RELEASE

卷:200

Article

Ishii-Mizuno, Yumiko¹  Umeki, Yuka¹  Takahashi, Yuki¹  Kato, Yukinori²  Takabayashi, Tetsuji²  Fujieda, Shigeharu²  Takakura, Yoshinobu¹  Nishikawa, Makiya¹ 

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut & Drug Metab, Sakyo Ku, Kyoto 6068501, Japan

[2] Univ Fukui, Fac Med Sci, Dept Sensory & Locomotor Med, Div Otorhinolaryngol Head & Neck Surg, Matsuoka, Fukui 9101193, Japan

关键词: Hydrogel;    CpG motif;    Controlled release;    Nasal delivery;    Allergen;    Self-gelling;   

DOI  :  10.1016/j.jconrel.2014.12.040

来源: Elsevier

【 摘 要 】

To develop an immunotherapeutic vaccine for treatment of allergic rhinitis, we developed a controlled release formulation of Cryj1, a major Japanese cedar pollen allergen, with immunostimulatory potency. Two sets of hexapod-like structured DNA (hexapodna) were prepared using six oligodeoxynucleotides (ODNs) each, including ODNs with an unmethylated cytosine-phosphate-guanine (CpG) sequence (CpG motif), to obtain an immunostimulatory DNA hydrogel (sDNA hydrogel). A non-immunostimulatory DNA hydrogel (nsDNA hydrogel) was also prepared using ODNs with no CpG motifs. The sDNA hydrogel was more effective than its components or the nsDNA hydrogel for production of interleukin (IL)-12 after addition to murine macrophage-like RAW264.7 cells or after intranasal administration to mice. Then, a Cryj1-loaded sDNA hydrogel (Cryj1/sDNA hydrogel) formulation was prepared by mixing solutions containing both Cryj1 and hexapodna. Cryj1 was slowly released from the sDNA hydrogel in phosphate-buffed saline. After intranasal administration of the fluorescein isothiocyanate (FITC)-labeled Cryj1/sDNA hydrogel in mice, FITC-Cryj1 was retained in the nasal cavity for a longer period than FITC-Cryj1 mixed with hexapodna in solution. Intranasal immunization of mice with the Cryj1/sDNA hydrogel resulted in high levels of Cryj1-specific IgG in nasal lavage fluid (NFL), IL-12 and interferon-gamma release from spleen cells after re-stimulation with Cryj1 when compared with intranasal immunization with the other formulations examined. These results indicate that the self-gelling immunostimulatory DNA hydrogel is an effective formulation for controlled induction of allergen-specific immune responses. (C) 2015 Elsevier B.V. All rights reserved.

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