Yousef Malaz, Park Chulhun, Henostroza Mirla, Bou Chacra Nadia, Davies Neal M, Löbenberg Raimar
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
College of Pharmacy, Jeju National University, Jeju 63243, Republic of Korea.
Pharmaceutics. 2023 Oct 26;15(11):2532. doi: 10.3390/pharmaceutics15112532.
The lymphatic system plays a crucial role in the absorption of lipophilic drugs, making it an important route for drug delivery. In this study, an in vitro model using Intralipid was developed to investigate the lymphatic uptake of drugs. The model was validated using cannabidiol, halofantrine, quercetin, and rifampicin. Remarkably, the uptake of these drugs closely mirrored what would transpire in vivo. Furthermore, adding peanut oil to the model system significantly increased the lymphatic uptake of rifampicin, consistent with meals containing fat stimulating lymphatic drug uptake. Conversely, the inclusion of pluronic L-81 was observed to inhibit the lymphatic uptake of rifampicin in the model. This in vitro model emerges as a valuable tool for investigating and predicting drug uptake via the lymphatic system. It marks the first phase in developing a physiologically based predictive tool that can be refined further to enhance the precision of drug interaction predictions with chylomicrons and their subsequent transport via the lymphatic system. Moreover, it can be employed to explore innovative drug formulations and excipients that either enhance or hinder lymphatic drug uptake. The insights gained from this study have significant implications for advancing drug delivery through the lymphatic system.
淋巴系统在亲脂性药物的吸收中起着关键作用,使其成为药物递送的重要途径。在本研究中,开发了一种使用英脱利匹特的体外模型来研究药物的淋巴摄取。该模型使用大麻二酚、卤泛群、槲皮素和利福平进行了验证。值得注意的是,这些药物的摄取情况与体内发生的情况极为相似。此外,向模型系统中添加花生油显著增加了利福平的淋巴摄取,这与含脂肪的膳食刺激淋巴药物摄取的情况一致。相反,观察到加入普朗尼克L - 81会抑制模型中利福平的淋巴摄取。这种体外模型成为研究和预测通过淋巴系统的药物摄取的有价值工具。它标志着开发基于生理学的预测工具的第一阶段,该工具可进一步完善以提高药物与乳糜微粒相互作用预测及其随后通过淋巴系统转运的精度。此外,它可用于探索增强或阻碍淋巴药物摄取的创新药物制剂和辅料。本研究获得的见解对推进通过淋巴系统的药物递送具有重要意义。