Nasal Delivery of Hesperidin/Chitosan Nanoparticles Suppresses Cytokine Storm Syndrome in a Mouse Model of Acute Lung Injury.
Nasal Delivery of Hesperidin/Chitosan Nanoparticles Suppresses Cytokine Storm Syndrome in a Mouse Model of Acute Lung Injury.
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橙皮苷/壳聚糖纳米颗粒的鼻递送可抑制急性肺损伤小鼠模型中的细胞因子风暴综合征
DOI：
10.3389/fphar.2020.592238
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发表时间：
2020
影响因子：
5.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Jin H;Zhao Z;Lan Q;Zhou H;Mai Z;Wang Y;Ding X;Zhang W;Pi J;Evans CE;Liu X
细胞因子风暴或细胞因子风暴综合征(CSS)与急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)患者的高死亡率相关，例如，脓毒症或包括新冠肺炎在内的感染性疾病。然而，目前还没有有效的治疗方法来治疗与CSS相关的ALI或ALI/ARDS。因此，仍然迫切需要开发有效的药物和治疗策略来对抗CS和ALI/ARDS。鼻腔和吸入给药方法是治疗炎症性肺部疾病的一种很有前途的策略，因为它们有能力改善对肺的药物输送。将黏膜生物利用度低的难于溶于水的药物的鼻黏膜吸收提高到治疗有效的水平是对抗ALI/ARDS的另一个有希望的策略。在这里，我们开发了橙皮苷壳聚糖纳米粒(HPD/NPs)，用于抗炎HPD化合物的鼻腔给药。在体外和体内，与游离HPD相比，HPD/NPs在炎症微环境中显示出更强的细胞摄取能力。在炎症性肺病小鼠模型中，与游离HPD相比，HPD/NPs显著抑制肺损伤，表现为炎性细胞因子水平降低和血管通透性抑制。总而言之，我们的研究表明，在炎症性肺疾病的小鼠模型中，HPD/NPs的鼻腔给药抑制了CS和ALI/ARDS，具有抗炎作用的纳米颗粒治疗策略可以用于减少炎症性肺损伤患者的CS和ALI。
The cytokine storm or cytokine storm syndrome (CSS) is associated with high mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), for example following sepsis or infectious diseases including COVID-19. However, there are no effective treatments for CSS-associated ALI or ALI/ARDS. Thus, there remains an urgent need to develop effective drugs and therapeutic strategies against CSS and ALI/ARDS. Nasal and inhaled drug delivery methods represent a promising strategy in the treatment of inflammatory lung disease as a result of their ability to improve drug delivery to lungs. Improving the nasal mucosa absorption of poorly water-soluble drugs with poor mucosa bioavailability to a therapeutically effective level is another promising strategy in the fight against ALI/ARDS. Here, chitosan nanoparticles loaded with hesperidin (HPD/NPs) were developed for nasal delivery of the anti-inflammatory HPD compound to inflammatory lungs. In vitro and in vivo, HPD/NPs exhibited enhanced cellular uptake in the inflammatory microenvironment compared with free HPD. In a mouse model of inflammatory lung disease, the HPD/NPs markedly inhibited lung injury as evidenced by reduced inflammatory cytokine levels and suppressed vascular permeability compared with free HPD. Collectively, our study demonstrates that nasal delivery of HPD/NPs suppresses CSS and ALI/ARDS in a murine model of inflammatory lung disease, and that nanoparticle-based treatment strategies with anti-inflammatory effects could be used to reduce CSS and ALI in patients with inflammatory lung injury.
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影响因子：
37.8
作者：
Huang X;Dai Z;Cai L;Sun K;Cho J;Albertine KH;Malik AB;Schraufnagel DE;Zhao YY
通讯作者：
Zhao YY
影响因子：
3.4
作者：
Li, Yongsheng;Kandhare, Amit D.;Bodhankar, Subhash L.
通讯作者：
Bodhankar, Subhash L.
影响因子：
3.8
作者：
Hemanth Kumar B;Dinesh Kumar B;Diwan PV
通讯作者：
Diwan PV
影响因子：
9
作者：
Channappanavar R;Perlman S
通讯作者：
Perlman S
影响因子：
7.6
作者：
Lin CW;Tsai FJ;Tsai CH;Lai CC;Wan L;Ho TY;Hsieh CC;Chao PD
通讯作者：
Chao PD