乳糜微粒
纳米晶
材料科学
人口
吸收(声学)
纳米技术
生物物理学
化学
医学
生物化学
脂蛋白
生物
环境卫生
胆固醇
极低密度脂蛋白
复合材料
作者
Xing Wang,Feiyang Deng,Te Ji,Chengning Zhang,Tian Yang,Jing Wang,Aiping Zheng,Ying Chen,Bing He,Wenbing Dai,Hua Zhang,Qiang Zhang,Xueqing Wang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-08-17
标识
DOI:10.1021/acsnano.4c05391
摘要
Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.
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