Chen Hsin-Hung, Sang Chen-Hsiang, Chou Chang-Wei, Lin Yi-Ting, Chang Yi-Shou, Chiu Hsin-Cheng
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of R&D, Medical Division, MicroBase Technology Corp, Taoyuan City 33464, Taiwan.
Pharmaceutics. 2024 Jun 29;16(7):878. doi: 10.3390/pharmaceutics16070878.
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.
肺炎是每年导致儿童死亡的主要感染原因，凸显了其对儿童健康的重大影响。尽管地塞米松（DXMS）对治疗肺部炎症有效，但其治疗潜力因全身副作用和不理想的载体系统而受到影响。为了解决这个问题，当前研究引入了包裹疏水性地塞米松棕榈酸酯（DXMS-Pal-SLNs）的固体脂质纳米颗粒作为治疗肺炎的抗炎纳米平台。这种特殊的纳米颗粒制剂具有高载药效率、低药物泄漏率以及出色的胶体稳定性，特别是在雾化过程中，并且经过精心设计，通过雾化给药实现局部递送，靶向肺部深处的肺泡巨噬细胞。体外分析显示，肺泡巨噬细胞分泌的肿瘤坏死因子-α和白细胞介素-6大幅减少，突出了DXMS-Pal-SLNs在减轻肺炎相关炎症方面的潜在疗效。同样，体内实验表明，通过雾化给予DXMS-Pal-SLNs后，脂多糖诱导的肺部炎症小鼠肺部这些细胞因子的水平显著降低。此外，该研究表明，DXMS-Pal-SLNs能有效控制急性感染，而不会导致肺组织中的肺部浸润或免疫细胞过度募集。这些发现凸显了雾化DXMS-Pal-SLNs作为减轻肺炎相关炎症的一种有前景的治疗策略的潜力。
