Hou Jingjing, Zhang Mengdi, Han Zheyi, Wang Wanmei, Qiu Haiying, Yuan Jingwei, An Fang, Wu Yan
Air Force Medical Center, PLA., Air Force Medical University, Beijing, China.
Department of Pharmacy, Hebei North University, Hebei Key Laboratory of Neuropharmacology, Zhangjiakou, China.
Int J Pharm X. 2025 Aug 20;10:100379. doi: 10.1016/j.ijpx.2025.100379. eCollection 2025 Dec.
Seawater drowning-induced acute lung injury (ALI) presents a significant challenge due to the lack of effective prevention and treatment strategies. Hesperidin (Hep) possesses diverse biological activities, including potent antioxidant and anti-inflammatory effects. However, its clinical utility is hindered by poor solubility and limited bioavailability. Therefore, there is an urgent need for the modification of hesperidin to enhance its water solubility and expand its therapeutic potential. In this study, an inhalable formulation of Hep-β-cyclodextrin inclusion complexes (Hep-β-CD) was developed as a promising approach for the management of seawater drowning-induced ALI. The cytotoxicity assessment in BEAS-2B cells revealed minimal adverse effects associated with Hep-β-CD. The administration of Hep-β-CD via the pulmonary route has been found to be highly effective in preventing seawater drowning-induced ALI in mice, achieved through modulation of key inflammatory mediators and a reduction in oxidative stress. The study demonstrated that Hep-β-CD administration significantly decreased the levels of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6), which are known to contribute to the pathogenesis of ALI. Additionally, the levels of malondialdehyde (MDA) were decreased and the levels of Superoxide Dismutase (SOD) were increased. In summary, the pulmonary delivery of Hep-β-CD was identified as a promising therapeutic strategy for preventing seawater drowning-induced ALI due to its ability to directly distribute the drug to the lungs, where it exerts a dual action of modulating the immune response to reduce inflammation and enhance the antioxidant defense mechanism.
由于缺乏有效的预防和治疗策略，海水溺水诱发的急性肺损伤（ALI）是一项重大挑战。橙皮苷（Hep）具有多种生物活性，包括强大的抗氧化和抗炎作用。然而，其临床应用受到溶解度差和生物利用度有限的阻碍。因此，迫切需要对橙皮苷进行修饰，以提高其水溶性并扩大其治疗潜力。在本研究中，开发了一种可吸入的橙皮苷-β-环糊精包合物（Hep-β-CD）制剂，作为治疗海水溺水诱发ALI的一种有前景的方法。在BEAS-2B细胞中的细胞毒性评估显示，Hep-β-CD的不良反应极小。通过肺部途径给予Hep-β-CD已被发现对预防小鼠海水溺水诱发的ALI非常有效，这是通过调节关键炎症介质和降低氧化应激来实现的。该研究表明，给予Hep-β-CD可显著降低促炎细胞因子如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平，已知这些细胞因子会导致ALI的发病机制。此外，丙二醛（MDA）水平降低，超氧化物歧化酶（SOD）水平升高。总之，Hep-β-CD的肺部给药被认为是预防海水溺水诱发ALI的一种有前景的治疗策略，因为它能够将药物直接输送到肺部，在肺部发挥双重作用，即调节免疫反应以减轻炎症并增强抗氧化防御机制。
