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布地奈德负载双分子层囊泡作为一种针对大鼠急性肺损伤的靶向递药治疗方法。

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats.

机构信息

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ahram Canadian University, 6(th) of October City, Cairo, Egypt.

出版信息

J Pharm Sci. 2023 Mar;112(3):760-770. doi: 10.1016/j.xphs.2022.10.001. Epub 2022 Oct 10.

Abstract

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-β contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19.

摘要

布地奈德(BUD)是一种糖皮质激素药物,可抑制炎症反应的所有步骤。它可以减轻和治疗与急性肺损伤相关的炎症和其他症状,如 COVID-19。将 BUD 载入双分子层囊泡中可以提高其治疗活性,并减少其频繁给药和副作用。我们制备了不同的双分子层囊泡制剂,其中自变量为脂质类型(胆固醇、磷脂酰胆碱 80H、L-α磷脂酰胆碱和 Lipoid S45)、胆汁盐类型(胆酸钠和脱氧胆酸钠)和药物浓度(10、20mg)。测量的响应是囊泡大小、包封效率和释放效率。选择了一种最佳制剂(由胆固醇、胆酸钠和 10mg BUD 组成),并在 Wistar 白化雄性大鼠体内研究其抗炎功效。将随机分配的大鼠分为四组:第一组:正常对照组,给予鼻腔生理盐水;第二组为急性肺损伤模型,给予鼻腔单剂量 2mg/kg 重铬酸钾(PD);第三组和第四组分别在 PD 滴注后 7 天内接受市售产品(Pulmicort®雾化混悬液 0.5mg/ml)和优化制剂(0.5mg/kg;鼻腔)。结果表明,优化制剂降低了肺中促炎细胞因子 TNF-α和 TGF-β的含量以及 PKC 的含量。这些发现表明,载有 BUD 的双分子层囊泡具有治疗急性肺损伤的潜力,并具有抑制 COVID-19 诱导的促炎细胞因子的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60b1/9549718/c34a2cd5b4ec/gr1_lrg.jpg

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