吸入皮质类固醇颗粒在沉积后的小气道吸收和微剂量学。
Small Airway Absorption and Microdosimetry of Inhaled Corticosteroid Particles after Deposition.
机构信息
Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, Virginia, 23284-3015, USA.
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA.
出版信息
Pharm Res. 2017 Oct;34(10):2049-2065. doi: 10.1007/s11095-017-2210-7. Epub 2017 Jun 22.
PURPOSE
To predict the cellular-level epithelial absorbed dose from deposited inhaled corticosteroid (ICS) particles in a model of an expanding and contracting small airway segment for different particle forms.
METHODS
A computational fluid dynamics (CFD)-based model of drug dissolution, absorption and clearance occurring in the surface liquid of a representative small airway generation (G13) was developed and used to evaluate epithelial dose for the same deposited drug mass of conventional microparticles, nanoaggregates and a true nanoaerosol. The ICS medications considered were budesonide (BD) and fluticasone propionate (FP). Within G13, total epithelial absorption efficiency (AE) and dose uniformity (microdosimetry) were evaluated.
RESULTS
Conventional microparticles resulted in very poor AE of FP (0.37%) and highly nonuniform epithelial absorption, such that <5% of cells received drug. Nanoaggregates improved AE of FP by a factor of 57-fold and improved dose delivery to reach approximately 40% of epithelial cells. True nanoaerosol resulted in near 100% AE for both drugs and more uniform drug delivery to all cells.
CONCLUSIONS
Current ICS therapies are absorbed by respiratory epithelial cells in a highly nonuniform manner that may partially explain poor clinical performance in the small airways. Both nanoaggregates and nanoaerosols can significantly improve ICS absorption efficiency and uniformity.
目的
为不同颗粒形态的扩张和收缩小气道模型预测吸入皮质类固醇（ICS）颗粒沉积后的细胞级上皮吸收剂量。
方法
开发了一种基于计算流体动力学（CFD）的药物溶解、吸收和清除模型，用于评估代表小气道一代（G13）的表面液体中相同沉积药物质量的常规微颗粒、纳米聚集体和真正纳米气溶胶的上皮剂量。所考虑的 ICS 药物为布地奈德（BD）和丙酸氟替卡松（FP）。在 G13 中，评估了总上皮吸收效率（AE）和剂量均匀性（微剂量学）。
结果
常规微颗粒导致 FP 的 AE 非常差（0.37%），上皮吸收极不均匀，<5%的细胞接受药物。纳米聚集体将 FP 的 AE 提高了 57 倍，并改善了药物输送，使约 40%的上皮细胞接受药物。真正的纳米气溶胶使两种药物的 AE 接近 100%，并使所有细胞的药物输送更加均匀。
结论
目前的 ICS 疗法以高度不均匀的方式被呼吸道上皮细胞吸收，这可能部分解释了在小气道中临床疗效不佳的原因。纳米聚集体和纳米气溶胶都可以显著提高 ICS 的吸收效率和均匀性。
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