Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 143, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2019.105172
Keywords
Allergen-specific immunotherapy; Celastrol; Polymeric nanomicelles; Allergic inflammation
Categories
Funding
- National Natural Science Foundation of China [81601395, 81871267]
- Excellent youth program of Shanghai General Hospital [06N1702008]
- Shanghai Sailing program [16YF1409200]
- Shanghai Jiao Tong University Medical and Industrial Cross Project [YG2015QN15]
- Shenkang's three-year action plan to promote clinical skills and clinical innovation capabilities in municipal hospitals [16CR3098B]
- Shanghai Science and Technology Commission Science and Technology Innovation Action Plan [19441904300]
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Allergies affect a significant proportion of the world's population, and existing vaccination strategies to restrict their adverse pathologies often render side-effects. The aim of this study was to design a new vaccine for allergen-specific immunotherapy (SIT), and to investigate its preventive effects during allergic inflammation. We constructed ovalbumin (OVA)-conjugated celastrol-loaded nanomicelles (OVA-NMs-celastrol), wherein celastrol (a bioactive anti-inflammatory compound) was loaded into carboxyl-functioned polymeric nanomicelles using a thin-film hydration method. OVA was used as a model allergen and conjugated on nanomicelles. The OVA-NMs-celastrol obtained were characterized based on particle size, morphology, drug encapsulation efficiency, and drug loading percentage. Further, the preventive effect of OVA-NMs-celastrol was evaluated in a mouse model of allergic asthma. Our results showed that OVA-NMs-celastrol possessed valuable characteristics such as small particle size (50.72 +/- 0.98 nm) and spherical-like shape, with celastrol encapsulation efficiency of 99.89 +/- 0.85% and a drug loading percentage of 4.76 +/- 0.03%. Further, in vivo results showed that treatment with OVA-NMs-celastrol could decrease OVA specific IgE and histamine levels, Th2 cytokine (IL-4, IL-5) levels, and inflammatory cell infiltration in the lung tissues. Moreover, it could enhance the OVA specific IgG1 and IgG2a levels and decrease the IgE / IgG2a ratio. These results demonstrate the successful construction of OVA-NMs-celastrol as a potential vaccine candidate for use in SIT for allergic inflammation.
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