Methods: Female, 6-week-old, BALB/c mice were intranasally administered 3 types of SNPs (spherical-type [S-SNPs], mesoporous-type [M-SNPs], and polyethylene glycol conjugated type [P-SNPs]) with or without ovalbumin (OVA), thrice weekly for 2 weeks. All mice were sacrificed 48 h after the last dose. We evaluated airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs.
Results: In the model administered SNPs alone, only M-SNPs induced significant AHR as compared to sham group, whereas all SNP-treated groups showed a significant increase in total cell, macrophage, and neutrophil counts in BALF. S-SNPs and M-SNPs induced an increase in cytokine (interleukin [IL]-5, IL-1β, and interferon-γ) levels. In the model administered SNPs with OVA, S-SNPs and M-SNPs induced significant AHR as compared to sham group and those administered OVA alone. Overall, greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL-1β, and IFN-γ) were observed in the group administered SNPs with OVA than those administered SNPs or OVA alone. However, P-SNPs induced lesser inflammation than the other types of SNPs in both models.
Conclusion: SNPs alone has significant toxic effectc on the airway system. Moreover, SNPs when administered with OVA cause adjuvant effects. We recommend the use of P-SNP because of its relative safety compared with S-SNP and M-SNP.