第一个以生理学为基础的药理动力学 (PBPK) 模型用于口服疫苗,使用阿尔法-托科菲罗尔作为辅助剂
Leonor Saldanha1,2,3, Nuno Vale1,2,3
1OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
Pharmaceutics
|September 28, 2023
概括
基于生理学上的药理动力学 (PBPK) 建模可以帮助口服疫苗的开发. 使用阿尔法-托科菲罗尔作为辅助剂的口服疫苗的新PBPK模型表明了最佳的配方策略.
科学领域:
- 疫苗学 疫苗学 疫苗学
- 药理动力学 药理动力学
- 药物运输 药物运输 药物运输
背景情况:
- 口服疫苗在管理和制造方面比传统疫苗具有优势.
- 基于生理学的药理动力学 (PBPK) 建模对于药物开发至关重要,但在疫苗研究中未得到充分利用.
- 阿尔法-托科菲罗尔是肌肉内疫苗的已知辅助剂,具有口服配方的潜力.
研究的目的:
- 为口服疫苗开发第一个PBPK模型,使用alpha-tocopherol作为辅助剂.
- 探索PBPK建模在优化口服疫苗设计中的应用.
- 确定使用alpha-tocopherol作为口服疫苗辅助剂的可行性.
主要方法:
- 构建一种用于口服疫苗的新型PBPK模型.
- 分析LogP作为影响alpha-tocopherol组织分布和代谢的关键参数.
- 鉴定口服疫苗疗效的关键配方参数.
主要成果:
- LogP显著影响alpha-tocopherol在脂肪组织中的输送和积累.
- 一个理想的口服疫苗配方包括囊中的纳米颗粒中的α-托科菲罗尔.
- 推剂量是150毫克的α-托科菲罗尔在一个200毫升的体积.
结论:
- PBPK建模为口服疫苗开发提供了有价值的框架.
- 阿尔法-托科菲罗尔可以有效地用作口服疫苗配方中的辅助剂.
- 优化的配方策略对于克服胃肠道挑战和确保抗原/辅助剂的输送至关重要.
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