Zhang Xingwang, Zhang Tianpeng, Zhou Xiaotong, Liu Hongming, Sun Hua, Ma Zhiguo, Wu Baojian
College of Pharmacy, Jinan University, Guangzhou, China.
J Pharm Sci. 2014 Jun;103(6):1711-9. doi: 10.1002/jps.23967. Epub 2014 Apr 2.
Oral delivery of anticancer drugs remains challenging because of limited water-solubility and/or poor permeability. Here, we aimed to enhance the oral bioavailability of tripterine (TRI, a plant-derived anticancer compound) using lipid nanospheres (LNs) and to determine the mechanisms of oral absorption. TRI-loaded LNs (TRI-LNs) were prepared by rapid dispersion of an ethanol mixture of TRI, lecithin, sodium oleate, and soybean oil into water. The obtained LNs were 150 nm in size with a high value of entrapment efficiency (99.95%). TRI-LNs were fairly stable and the drug release was negligible (<0.2%) in simulated physiological fluid. The pharmacokinetic results showed that LNs significantly enhanced the oral bioavailability of TRI with a relative bioavailability of 224.88% (TRI suspensions was used as a reference). The mechanistic studies demonstrated that improved intestinal permeability and post-enterocyte lymphatic transport were mainly responsible for the enhanced oral absorption. Our findings suggested that LNs may be a viable oral carrier for poorly bioavailable drugs.
由于水溶性有限和/或渗透性差，口服抗癌药物仍然具有挑战性。在此，我们旨在使用脂质纳米球（LNs）提高雷公藤红素（TRI，一种植物来源的抗癌化合物）的口服生物利用度，并确定口服吸收的机制。通过将TRI、卵磷脂、油酸钠和大豆油的乙醇混合物快速分散到水中来制备载TRI的LNs（TRI-LNs）。所获得的LNs尺寸为150 nm，包封率高（99.95%）。TRI-LNs相当稳定，在模拟生理流体中的药物释放可忽略不计（<0.2%）。药代动力学结果表明，LNs显著提高了TRI的口服生物利用度，相对生物利用度为224.88%（以TRI悬浮液作为对照）。机制研究表明，肠道通透性的改善和肠细胞后淋巴转运是口服吸收增强的主要原因。我们的研究结果表明，LNs可能是生物利用度差的药物的一种可行的口服载体。
