College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Experimental Teaching and Practical Training Center, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Int J Biol Macromol. 2024 Jul;273(Pt 2):133063. doi: 10.1016/j.ijbiomac.2024.133063. Epub 2024 Jun 14.
The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.
阿霉素（DOX）是一种抗癌药物，经口服给药时会遇到多种障碍，如有限的胃肠道通透性、P-糖蛋白介导的外排、短暂的肠道停留时间和快速降解。本研究介绍了一种利用透明质酸（HA）接枝脂肪酸单甘油酯（HGD）包载 DOX 形成 HGD-DOX 纳米粒的新方法，旨在提高其口服生物利用度。用 HGD 包封的药物具有多种优势，包括延长药物在胃肠道中的滞留时间、控制释放动力学以及促进肠道中的淋巴吸收。此外，HGD-DOX 纳米粒还可以特异性靶向 CD44 受体，从而可能提高治疗效果。HGD-DOX 纳米粒的摄取机制主要涉及网格蛋白介导、小窝蛋白介导和巨胞饮内吞作用。药代动力学分析进一步表明，HGD 显著延长了 DOX 的体内停留时间。体内成像和药效学研究表明，HGD 具有肿瘤靶向能力，并对肿瘤生长表现出显著的抑制作用，同时保持可接受的安全性。总的来说，这些发现表明 HGD-DOX 纳米粒是提高 DOX 口服生物利用度的一种有前途的策略，为改善癌症治疗提供了一种潜在途径。
