He Wenli, Yan Meng, Li Yue, Wang Jianchao, Yang Jianing, He Chaoxing, Yang Shaokun, Cao Deying, Bai Jing, Wang Lei, Xiang Bai
Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, PR China.
Key Laboratory of Hebei Province for Innovative Drug Research and Evaluation, Shijiazhuang 050017, PR China.
Int J Pharm X. 2025 Jul 10;10:100356. doi: 10.1016/j.ijpx.2025.100356. eCollection 2025 Dec.
Cancer remains a critical global health challenge with increasing incidence rates. This study reports the first successful encapsulation of glytrexate (GTX), a novel 6-substituted-pyrrolo [2,3-d] pyrimidine compound, into liposomes. This innovative formulation increases the stability, half-life, and bioavailability of GTX while significantly reducing toxicity. GTX liposomes, with a uniform spherical shape and an average particle size of 121.7 ± 2.9 nm, demonstrated a satisfactory encapsulation efficiency (24.2 ± 0.99 %). Compared to the free drug, GTX liposomes exhibited significantly enhanced inhibitory effects on 4 T1, A549, and MCF-7 cells in vitro. The pharmacokinetic analysis showed prolonged circulation (T: 3.82 h vs. 1.86 h) and increased systemic exposure (AUC: 31975.79 vs. 11,545.86 μg·h/L). In vivo studies further confirmed their efficacy, as they substantially reduced tumour growth by 50 %, decreasing lung metastasis in 4 T1 cell models, and minimizing GTX-related side effects. These findings highlight the potential of liposomal GTX formulations to improve breast cancer treatment outcomes.
癌症仍然是一个严峻的全球健康挑战，发病率不断上升。本研究报告了首次成功将新型6-取代-吡咯并[2,3-d]嘧啶化合物格列甲酸酯（GTX）包裹于脂质体中。这种创新制剂提高了GTX的稳定性、半衰期和生物利用度，同时显著降低了毒性。GTX脂质体呈均匀球形，平均粒径为121.7±2.9nm，表现出令人满意的包封率（24.2±0.99%）。与游离药物相比，GTX脂质体在体外对4T1、A549和MCF-7细胞表现出显著增强的抑制作用。药代动力学分析显示循环时间延长（T：3.82小时对1.86小时）和全身暴露增加（AUC：31975.79对11545.86μg·h/L）。体内研究进一步证实了它们的疗效，因为它们使肿瘤生长大幅减少50%，在4T1细胞模型中减少了肺转移，并将与GTX相关的副作用降至最低。这些发现突出了脂质体GTX制剂改善乳腺癌治疗效果的潜力。
