Abstract
Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations.