抗逆转录病毒 (ARV) 特性决定了多药性皮下植入物中的长效释放和组织分区行为
Jamie L Hernandez1, Shin-Tian Chien1, My-Anh Doan1
1Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States.
ACS biomaterials science & engineering
|September 4, 2024
概括
提供多种HIV药物的皮下植入物显示出基于药物特性的多种释放. 像埃特拉维林这样的疏水药物集中在预防艾滋病毒至关重要的组织中,突出显示了长效植入物药物特性的重要性.
科学领域:
- 生物医学工程 生物医学工程
- 药物输送系统 药物输送系统
- 预防传染病 预防传染病
背景情况:
- 皮下植入物为预防人类免疫缺陷病毒 (HIV) 提供长效,不依赖合规的药物输送.
- 配制具有多种抗逆转录病毒 (ARV) 候选物的多药物植入物,由于不同的物理化学性质,存在重大挑战.
研究的目的:
- 评估用于预防艾滋病毒的三种ARV的多药物输送的电纤维植入物.
- 为了研究药物特性对释放动力学和组织分布 in vivo 的影响.
主要方法:
- 用三种ARV和一种可生物降解的聚合物制成的电纤维植入物的配方.
- 在体外释放研究中选择合适的聚合物和药物组合.
- 在体内评估药物释放,血清度和小鼠在120天内组织分布.
主要成果:
- 电植入物表现出药物特定的释放特征,其中水友性药物 (maraviroc, raltegravir) 显示出初始爆发释放.
- 洗前处理减少了水友性药物的突发释放.
- 厌水药埃特拉维林在植入物,皮肤,淋巴结和生殖组织中表现出持续释放和高度.
结论:
- 药物释放和植入物中的组织分离主要由个体药物特性来决定.
- 埃特拉维林的物理化学特性有助于其在HIV保护的关键组织中积累.
- 长效植入物的未来开发应该优先考虑药物特性和针对目标和持续释放的前药物策略.
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