Abstract：
Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study\'s goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine\'s release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.
摘要：
非洛地平已被证明作为动脉粥样硬化疗法是有效的，因为它增加了流向血管壁的血液。然而,溶解性差，低生物利用度，口服非洛地平的肝脏首过代谢损害了其治疗效果。该研究的目标是创建一个鼻腔pH敏感的水凝胶的非洛地平加载的侵入体（IPHFI），将提高非洛地平的释放，渗透，生物利用度，以及作为潜在的糖尿病相关动脉粥样硬化疗法的有效性。根据配方前的研究，由磷脂（3％w/v）组成的非洛地平加载的侵入体制剂，胆固醇（0.16%w/v），选择乙醇（3％v/v）和桉树脑（1％v/v）作为最佳配方。在体外表征最佳制剂,然后与壳聚糖和单油酸甘油酯的混合物混合以制备IPHFI制剂。IPHFI制剂将非洛地平的释放和渗透提高了2.99倍和3倍，分别。为了评估IPHFI制剂的功效和生物利用度，使用实验性动脉粥样硬化大鼠模型进行了体内研究。与口服游离非洛地平相比，经鼻施用IPHFI制剂可使生物利用度增加3.37倍，并降低血清胆固醇，甘油三酯，LDL,钙化评分分别为1.56、1.53、1.80和1.18，分别。因此，经鼻IPHFI制剂可能代表有希望的糖尿病相关动脉粥样硬化治疗。
