Preventive effects of "ovalbumin-conjugated celastrol-loaded nanomicelles'' in a mouse model of ovalbumin-induced allergic airway inflammation

• Published in: European journal of pharmaceutical sciences 2020-02, Vol.143, p.105172, Article 105172
• Main Authors: Peng, Xia, Liang, Yuting, Li, Jia, Lin, Lihui, Wang, Juan, Yin, Yue, Liao, Huanjin, Li, Li
• Format: Article
• Language: English
• Subjects: Allergen-specific immunotherapy; Allergens - administration & dosage; Allergic inflammation; Animals; Asthma - blood; Asthma - drug therapy; Asthma - immunology; Asthma - pathology; Bronchoalveolar Lavage Fluid - immunology; Celastrol; Cytokines - immunology; Disease Models, Animal; Eosinophils - immunology; Female; Histamine Release; Immunoglobulin E - blood; Immunoglobulin G - blood; Lung - drug effects; Lung - immunology; Lung - pathology; Mice, Inbred BALB C; Micelles; Nanostructures - administration & dosage; Ovalbumin - administration & dosage; Ovalbumin - immunology; Polymeric nanomicelles; Triterpenes - administration & dosage
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.105172

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. [Display omitted]