School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Drug Deliv. 2021 Dec;28(1):1664-1672. doi: 10.1080/10717544.2021.1960928.
The intestinal capillary pathway is the most common way to absorb oral drugs, but for drugs with poor solubility and permeability and high first-pass metabolism, this pathway is very inefficient. Although intestinal lymphatic transport of lipophilic drugs or prodrugs is a promising strategy to improve the oral delivery efficiency of these drugs. The prodrug strategy for modifying compounds with Log > 5 to promote intestinal lymphatic transport is a common approach. However, transport of poor liposoluble compounds (Log < 0) through intestinal lymph has not been reported. Herein, triglyceride-mimetic prodrugs of scutellarin were designed and synthesized to promote intestinal lymphatic transport and increase oral bioavailability. Lymphatic transport and pharmacokinetic experiments showed that two prodrugs did promote intestinal lymphatic transport of scutellarin and the relative oral bioavailability was 2.24- and 2.45-fold of scutellarin, respectively. In summary, triglyceride-mimetic prodrugs strategy was used for the first time to study intestinal lymphatic transport of scutellarin with Log < 0, which could further broaden the application range of drugs to improve oral bioavailability with the assistance of intestinal lymphatic transport.
肠腔毛细血管途径是口服药物吸收的最常见途径，但对于那些溶解度和通透性差、首过代谢率高的药物，这种途径的效率非常低。尽管亲脂性药物或前药的肠淋巴转运是提高这些药物口服递送效率的有前途的策略，但将 Log > 5 的化合物修饰为前药以促进肠淋巴转运是一种常见的方法。然而，尚未有报道表明较差的脂溶性化合物（Log < 0）通过肠淋巴的转运。在此，设计并合成了灯盏乙素的甘油三酯模拟前药，以促进肠淋巴转运并提高口服生物利用度。淋巴转运和药代动力学实验表明，两种前药确实促进了灯盏乙素的肠淋巴转运，其相对口服生物利用度分别是灯盏乙素的 2.24 倍和 2.45 倍。综上所述，首次使用甘油三酯模拟前药策略来研究 Log < 0 的灯盏乙素的肠淋巴转运，这可以进一步拓宽药物的应用范围，借助肠淋巴转运来提高口服生物利用度。
