Abou-Taleb Heba A, Aldosari Basmah Nasser, Zaki Randa Mohammed, Afzal Obaid, Tulbah Alaa S, Shahataa Mary Girgis, Abo El-Ela Fatma I, Salem Heba F, Fouad Amr Gamal
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Merit University (MUE), Sohag 1646080, Egypt.
Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Pharmaceutics. 2023 Aug 30;15(9):2242. doi: 10.3390/pharmaceutics15092242.
Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic aria and stops the infarct core from growing. However, low bioavailability, a short biological half-life, and first-pass hepatic metabolism reduce the therapeutic efficacy of oral isoxsuprine. Therefore, the authors focused on developing isoxsuprine-loaded liposomes containing ethanol and propylene glycol (ILEP) formulation as nasal drops for the treatment of ischemic stroke in diabetic patients. Different ILEP formulations were optimized using Design Expert software, and the selected formulation was examined in vivo for its anti-stroke effect using a rat model of diabetes and stroke. The optimized ILEP, composed of 15% propylene glycol, 0.16% cholesterol, 10% ethanol, and 3.29% phospholipid, improved the sustainability, permeation, and targeting of isoxsuprine. Furthermore, the in vivo studies verified the improved neurological behavior and decreased dead shrunken neurons and vascular congestion of the rats treated with the optimized ILEP formulation, demonstrating its anti-stroke activity. In conclusion, our study found that treatment with an optimized ILEP formulation prevented the initiation and severity of stroke, especially in diabetic patients.
缺血性中风是第二大致死原因。高血糖是糖尿病的特征，会导致内皮功能障碍的发展并增加中风风险。异舒普林是一种有效的β-肾上腺素能激动剂，可改善缺血区域的血流并阻止梗死核心扩大。然而，低生物利用度、短生物半衰期和首过肝代谢降低了口服异舒普林的治疗效果。因此，作者专注于开发含有乙醇和丙二醇的载异舒普林脂质体（ILEP）制剂作为滴鼻剂，用于治疗糖尿病患者的缺血性中风。使用Design Expert软件优化了不同的ILEP制剂，并使用糖尿病和中风大鼠模型在体内检查了所选制剂的抗中风效果。由15%丙二醇、0.16%胆固醇、10%乙醇和3.29%磷脂组成的优化ILEP提高了异舒普林的可持续性、渗透性和靶向性。此外，体内研究证实，用优化的ILEP制剂治疗的大鼠神经行为得到改善，死亡萎缩神经元和血管充血减少，证明了其抗中风活性。总之，我们的研究发现，用优化的ILEP制剂治疗可预防中风的发生和严重程度，尤其是在糖尿病患者中。
