本研究旨在评估吉西他滨（GEM）/紫杉醇（PTX）共同负载于基于卵磷脂的自制纳米乳化预浓缩剂（LBSNEP），以口服口服实现节律治疗方式对胰腺癌的疗效。LBSNEP由壬酸甘油酯90、Tween80、卵磷脂、TPGS和丙基二醇按20:20:30:5:25的比例制备和评估，结果显示其粒径约为180纳米。对MIA PaCa-2进行的细胞存活研究表明，在PTX和GEM的比例达到1:2时具有协同效应。此外，LBSNEP和黄芩素（BAI）还能够防止GEM被胞嘧啶脱氨酶脱氨。在模拟胃液中，LBSNEP中GEM、PTX和BAI的组合显示出良好的溶解性。对大鼠进行的药代动力学研究表明，与溶液组相比，LBSNEP中GEM、PTX和BAI的联合给药提高了GEM和PTX的相对口服生物利用度分别为1.5倍和2倍。肿瘤抑制研究以节律疗法每日低剂量与传统疗法每3天较高剂量进行。结果表明，GEM/PTX/BAI LBSNEP的口服节律给药能够在给药阶段抑制肿瘤生长，并且与传统化疗相比，即使节律化疗剂量比后者低2.2倍，在第28天时肿瘤容积相似。综上所述，用于胰腺癌的口服GEM、PTX和BAI的自制纳米乳化药物传递系统以节律方式增强了治疗效果，为化疗提供了一种替代选择。版权所有©2023 Elsevier B.V. 发表。

This study aimed to evaluate gemcitabine (GEM)/paclitaxel (PTX) co-loaded into a lecithin-based self-nanoemulsifying preconcentrate (LBSNEP) orally administered in a metronomic therapeutic manner against pancreatic cancer. LBSNEP was developed and evaluated, composed of Caproyl 90, Tween80, lecithin, TPGS, and propyl glycol at a ratio of 20:20:30:5:25, resulting in a droplet diameter of approximately 180 nm. Cell viability studies on MIA PaCa-2 demonstrated a synergetic effect at a proportion of 1:2 between PTX and GEM. Additionally, LBSNEP and baicalein (BAI) were demonstrated to prevent GEM from being deaminated by cytidine deaminase. The combination of GEM, PTX, and BAI in the LBSNEP showed good dissolution in simulated gastric fluid. The pharmacokinetic study conducted on rats showed that co-administration of GEM, PTX, and BAI in the LBSNEP enhanced the respective relative oral bioavailability levels of GEM and PTX by 1.5- and 2-fold, respectively, compared to the solution group. The tumor inhibition study was conducted with metronomic therapy at a low daily dose compared to conventional therapy at a higher dose every 3 days. Results indicated that oral metronomic delivery of GEM/PTX/BAI LBSNEP could inhibit tumor growth during administration phase, and that there were similar tumor volumes compared to traditional chemotherapy at day 28 even if the dose of metronomic chemotherapy was 2.2-fold less than that of the latter. In conclusion, a self-nanoemulsifying drug-delivery system for the oral delivery of GEM, PTX, and BAI in a metronomic manner enhanced the therapeutic effect on pancreatic cancer, providing an alternative option for chemotherapy.Copyright © 2023. Published by Elsevier B.V.