基于黄瓜[7]尿素的宿主-客人复合体,用于提高皮罗西卡姆的生物可用性和减少皮罗西卡姆副作用
Yan Wang1, Xiaodi Yang1, Jianguo Luo1
1College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.
International journal of pharmaceutics
|June 19, 2024
概括
黄瓜[7]uril (CB[7]) 显著增强了抗炎药物皮洛克萨姆 (PX) 的输送,改善了生物可用性并减少了胃部的副作用. 这种新的配方 (PX@CB[7]) 为炎症条件提供了更安全,更有效的治疗选择.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 药用化学 医学化学
背景情况:
- 皮洛西卡姆 (PX) 是一种非类固醇抗炎药物 (NSAID),由于其溶解性有限,经常导致胃肠道 (GI) 损伤.
- 现有配方使用β-cyclodextrin (β-CD) 显示适度改善溶解性和溶解性,但仍然导致常见的不良反应.
- PX和β-CD之间的低结合亲和度限制了可溶性增强的程度.
研究的目的:
- 调查Cucurbit[7]uril (CB[7]) 作为Piroxicam (PX) 配方的优质宿主分子的潜力.
- 评估CB[7]复合对PX的溶解性,溶解率,口服生物可用性和抗炎疗效的影响.
- 为了评估与CB配制的PX的胃肠道安全性,与单独的PX和与β-CD配制的PX相比[7].
主要方法:
- 在模拟的胃环境中将PX与CB复合[7]并确定结合常数.
- 在PX,PX@CD和PX@CB[7]配方溶解速度的体外评估.
- 在体内评估口服生物可用性,最大度 (Cmax),在小鼠和老鼠模型中的抗炎作用,以及胃粘膜粘附.
- 亚急性毒性研究,以评估CB的口服生物相容性[7].
主要成果:
- CB[7]形成PX包容复合体 (PX@CB[7]),其结合常数大约是PX的β-CD的70倍.
- 在胃条件下,PX@CB[7] 呈现出快速溶解率.
- PX@CB[7]显著提高了口服生物可用性和Cmax,从而改善了动物模型中的抗炎活性.
- 与PX和PX@CD配方相比,PX@CB[7] (1:2.5) 显示了最小的胃粘膜粘附和最轻微的胃肠道副作用.
- 在毒性研究中,CB [7] 呈现出良好的口服生物相容性.
结论:
- CB[7]是皮洛西卡姆的高效宿主分子,显著提高了其溶解性,生物可用性和治疗效果.
- PX@CB[7]配方提供了一种有希望的策略,以减轻NSAID诱导的胃肠毒性.
- CB[7]具有良好的安全性,表明其作为开发更安全,更有效的口服药物配方的有价值辅助剂的潜力.
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