通过共同形态系统增强口服巴佐帕尼布的生物可用性:配方,表征,药理动力学和毒性评估
Khushi Rode1, Indrani Maji1, Anish Dhuri1
1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research , (NIPER), Hyderabad, Telangana 500037, India.
Colloids and surfaces. B, Biointerfaces
|August 19, 2025
概括
这项研究开发了一种Pazopanib Naringin同形系统 (PZ-NGN-CAM),以提高Pazopanib (PZ) 的生物可用性并降低肝毒性. 这种新型的共同形态系统证明了更好的溶解性,透性和体内生物可用性,为癌症治疗提供了有前途的替代疗法.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 帕佐帕尼布 (PZ) 是一种氨酸激酶抑制剂,是细胞癌的第一线治疗方法.
- PZ具有较低的溶解性,生物可用性较差,肝毒性显著,限制了其治疗疗效.
- 纳林因 (NGN) 是一种天然的黄类化合物,具有玻璃形成能力和P-gp抑制潜力,使其成为合适的辅助形成剂.
研究的目的:
- 改善巴佐帕尼布 (PZ) 的生物利用性和降低肝毒性.
- 为了制造一个新的Pazopanib Naringin同形系统 (PZ-NGN-CAM),使用naringin (NGN) 作为同形.
- 评估已开发的共形系统的物理化学,体外和体内特征.
主要方法:
- 用分子对接和粉末X射线衍射 (PXRD) 来证实NGN与PZ共形系统形成的潜力.
- 固态特征包括差分扫描热量计 (DSC),PXRD,富里埃变换红外光谱 (FTIR) 和扫描电子显微镜 (SEM).
- 进行了体外溶解,表面透性 (Papp) 研究和体内药理动力学评估.
主要成果:
- 在PZ-NGN-CAM内部的无形性和分子间相互作用通过固态表征和NMR研究得到证实.
- 与PZ相比,PZ-NGN-CAM的溶解度在pH 6.8时增加了2.87倍,在pH 1.2时增加了1.85倍.
- 实验室研究显示药物释放速度快,表面透率提高2.23倍,体内生物利用率提高1.26倍.
结论:
- 开发的Pazopanib Naringin Co-amorphous系统 (PZ-NGN-CAM) 显著提高了pazopanib的可溶性,透性和生物可用性.
- 在急性毒性研究中,PZ-NGN-CAM表现出显著的肝保护作用.
- 该PZ-NGN-CAM配方为改善pazopanib在癌症治疗中的治疗潜力提供了一个有希望的替代方案.
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