纳米晶体在改善难溶性药物的口服生物利用度方面表现出显著优势。然而,纳米晶体复杂的吸收特性以及儿童和成人之间生理特性的差异限制了纳米晶体的儿科应用。为了阐明儿童和成人之间的吸收差异和潜在的机制,研究了不同粒径的阿瑞吡坦晶体(NC200,NC500和MC2.5)在不同年龄的大鼠和小鼠体内的药代动力学和组织分布,并在Caco-2细胞中研究了它们的吸收机制,老鼠,和老鼠。发现与青春期和成年动物相比,童年动物表现出更高的生物利用度,这与较高的胆汁盐浓度和儿童动物肠道中药物溶解加速有关。在胆汁盐的影响下,大多数纳米晶体溶解并形成胶束。与完整的纳米晶体相比,胆汁盐胶束相关的阿瑞吡坦通过乳糜微粒途径被吸收,其中ApoB在胞吞后辅助阿瑞吡坦胶束的重组。儿童动物肠道中较高的胆汁盐浓度和ApoB表达都是较高的乳糜微粒转运途径的原因。阐明儿童对纳米晶体的不同吸收中的乳糜微粒途径,青少年,为促进儿童人群合理、安全使用纳米晶体提供了有力的理论指导。
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.