School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK; Tri-Service General Hospital, Medical Supplies and Maintenance Office, National Defense Medical Center, Taipei, Taiwan.
Eur J Pharm Biopharm. 2021 May;162:43-49. doi: 10.1016/j.ejpb.2021.02.013. Epub 2021 Mar 5.
Lipid-based formulations play a significant role in oral delivery of lipophilic drugs. Previous studies have shown that natural sesame oil promotes the intestinal lymphatic transport and oral bioavailability of the highly lipophilic drug cannabidiol (CBD). However, both lymphatic transport and systemic bioavailability were also associated with considerable variability. The aim of this study was to test the hypothesis that pre-digested lipid formulations (oleic acid, linoleic acid, oleic acid with 2-oleoylglycerol, oleic acid with 2-oleoylglycerol and oleic acid with glycerol) could reduce variability and increase the extent of the intestinal lymphatic transport and oral bioavailability of CBD. The in vivo studies in rats showed that pre-digested or purified triglyceride did not improve the lymphatic transport and bioavailability of CBD in comparison to sesame oil. Moreover, the results suggest that both the absorption of lipids and the absorption of co-administered CBD were more efficient following administration of natural sesame oil vehicle compared with pre-digested lipids or purified trioleate. Although multiple small molecule constituents and unique fatty acid compositions could potentially contribute to a better performance of sesame oil in oral absorption of lipids or CBD, further investigation will be needed to identify the mechanisms involved.
脂质体制剂在亲脂性药物的口服递送上起着重要作用。先前的研究表明,天然芝麻油促进了高度亲脂性药物大麻二酚(CBD)的肠道淋巴转运和口服生物利用度。然而,淋巴转运和全身生物利用度也与相当大的可变性有关。本研究旨在检验以下假设:预先消化的脂质制剂(油酸、亚油酸、含有 2-油酰基甘油的油酸、含有 2-油酰基甘油和油酸的甘油)可以降低变异性并增加 CBD 的肠道淋巴转运和口服生物利用度。在大鼠体内研究中,与芝麻油相比,预先消化或纯化的三酸甘油酯并不能改善 CBD 的淋巴转运和生物利用度。此外,结果表明,与预先消化的脂质或纯化的三油酸酯相比,天然芝麻油载体给药后,脂质和同时给予的 CBD 的吸收更有效。尽管多种小分子成分和独特的脂肪酸组成可能有助于芝麻油在脂质或 CBD 的口服吸收中发挥更好的作用,但需要进一步研究以确定涉及的机制。