提升里托纳维尔装载纳米结构脂质载体的组织分布,建议降低其剂量
Srinivas Reddy Jitta1, Salwa1, Navya Ajitkumar Bhaskaran1
1Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576 104, Udupi, Karnataka, India.
载有里托纳维尔的纳米结构脂质载体 (RTV-NLCs) 显示出对HIV治疗的淋巴系统吸收有前途. 这些RTV-NLC在动物模型中显示出良好的安全性和有效性,这表明改善HIV治疗的潜力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 纳米技术纳米技术
- 免疫学 免疫学 免疫学
背景情况:
- 人类免疫缺陷病毒 (HIV) 向淋巴细胞,导致获得性免疫缺陷综合征 (AIDS).
- 利托纳维尔 (RTV),一种蛋白酶抑制剂 (PI),在高活性抗逆转录病毒疗法 (HAART) 中对于艾滋病毒治疗至关重要.
- 向淋巴系统 (LS) 对于保持艾滋病毒储存库中的治疗药物度至关重要.
研究的目的:
- 评估RTV载荷纳米结构脂质载体 (RTV-NLCs) 的细胞毒性和淋巴系统输送.
- 在动物模型中评估RTV-NLCs的生物分布和安全概况.
主要方法:
- 在HepG2,MEK293和H9C2细胞系中使用MTT测定来评估细胞毒性.
- 淋巴系统吸收在Wistar大鼠中使用注射循环赫西米德的基洛米克朗流量阻塞模型进行了评估.
- 在动物中进行了生物分布和毒性研究.
主要成果:
- 在RTV-NLC中,细胞活力与纯RTV-API相比相当.
- 在接受RTV-NLC治疗的组与没有注射循环赫西米德之间观察到AUC的>2.5倍差异.
- 生物分布研究显示,在没有显著肝毒性标志物的淋巴细胞器官中,RTV-NLC暴露率较高.
结论:
- 在动物中,RTV-NLCs显示有效的淋巴吸收和有利的安全概况.
- 与RTV-API相比,优化RTV-NLC剂量可能会提高HIV治疗的安全性和有效性.
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