Ragab Tamer I M, Kassem Abdulsalam M, Abdallah Heba M I, El Awdan Sally A, Ammar Naglaa M, El Gendy Abd El-Nasser G, Aboulhoda Basma Emad, Afifi Sherif M, Esatbeyoglu Tuba, Omara Enayat A, Elshamy Abdelsamed I
Chemistry of Natural and Microbial Products Department, National Research Centre, Dokki, Cairo, Egypt.
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.
PLoS One. 2025 Jul 11;20(7):e0327368. doi: 10.1371/journal.pone.0327368. eCollection 2025.
Innovative treatment strategies are required for stomach ulcers because of their multifactorial nature. Nanotechnology has emerged as a promising and transformative platform for the formulation and targeted delivery of therapeutic agents.
The gastroprotective potential of both in its free form and encapsulated in calcium alginate beads was evaluated against ethanol-induced gastric ulceration in rats. Phytol-loaded nanoemulsions were incorporated into alginate beads to achieve controlled release. Alginate beads showed a pH-dependent release pattern. The release behavior showed a higher release rate at pH 6.8 than at pH 1.2. Phytol release kinetics followed the Korsmeyer-Peppas model, indicating a release mechanism governed by diffusion and polymer relaxation. Rats were pretreated with Phytol and/or nano-Phytol at 10 or 20 mg/kg doses administered one hour before ethanol exposure. Gastric ulcer was induced by administration of EtOH (1 mL/kg, p.o.) 0.5 h after NG-nitro-L-Arginine Methyl Ester (L-NAME) or Aminoguanidine (AMG) injection. Phytol treatment led to a reduction in ulcer index and severity and improved stomach gross morphology. Also, interleukin-6 (IL-6) gastric contents were reduced, whereas transforming growth factor β (TGF-β1) was elevated, and histopathological features were ameliorated. Western blot analysis revealed that nano-Phytol exerted greater inhibitory effects on caspase-3 and Nuclear Factor kappa B (NF-κB) than unformulated Phytol. Interestingly, Phytol's pharmacological effects on ulcers were enhanced by its nanoformulation in a dose-dependent way without exhibiting any toxicity symptoms. Confocal laser scanning microscopy (CLSM) confirmed significantly improved tissue penetration of nano-Phytol within the stomach layers compared to the Phytol. The Phytol or nano-Phytol gastroprotective effects were modified via the co-administration of L-NAME and AMG.
The nano-Phytol formulation significantly enhanced the gastroprotective effect of Phytol against ethanol-induced gastric ulcers, primarily through modulation of the nitric oxide (NO) synthase pathway, suppression of inflammation, and upregulation of the growth factor TGF-β1.
由于胃溃疡具有多因素性质，因此需要创新的治疗策略。纳米技术已成为一种有前景的变革性平台，用于治疗剂的制剂和靶向递送。
评估了游离形式的以及包封在海藻酸钙珠中的植物醇对大鼠乙醇诱导的胃溃疡的胃保护潜力。将负载植物醇的纳米乳剂掺入海藻酸珠中以实现控释。海藻酸珠呈现出pH依赖性释放模式。释放行为在pH 6.8时的释放速率高于pH 1.2时。植物醇释放动力学遵循Korsmeyer-Peppas模型，表明释放机制受扩散和聚合物松弛控制。在乙醇暴露前1小时，以10或20 mg/kg的剂量用植物醇和/或纳米植物醇对大鼠进行预处理。在注射NG-硝基-L-精氨酸甲酯（L-NAME）或氨基胍（AMG）0.5小时后，通过给予乙醇（1 mL/kg，口服）诱导胃溃疡。植物醇治疗导致溃疡指数和严重程度降低，并改善了胃大体形态。此外，胃内容物中的白细胞介素-6（IL-6）减少，而转化生长因子β（TGF-β1）升高，并且组织病理学特征得到改善。蛋白质印迹分析显示，纳米植物醇对半胱天冬酶-3和核因子κB（NF-κB）的抑制作用比未配制的植物醇更大。有趣的是，植物醇的纳米制剂以剂量依赖性方式增强了其对溃疡的药理作用，且未表现出任何毒性症状。共聚焦激光扫描显微镜（CLSM）证实，与植物醇相比，纳米植物醇在胃层内的组织穿透性显著提高。通过联合给予L-NAME和AMG改变了植物醇或纳米植物醇的胃保护作用。
纳米植物醇制剂显著增强了植物醇对乙醇诱导的胃溃疡的胃保护作用，主要是通过调节一氧化氮（NO）合酶途径、抑制炎症以及上调生长因子TGF-β1来实现的。
