Wang Rongrong, Yang Jiaqi, Qiang Jihong, Li Qingxia, Wang Geng, Ping Canqi, Liu Kesheng, Wang Ruili, Zheng Bin, Ren Guolian, Zhang Shuqiu
School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China.
Int J Pharm X. 2025 Jul 31;10:100370. doi: 10.1016/j.ijpx.2025.100370. eCollection 2025 Dec.
Although malaria has been effectively controlled, it still poses a threat to global health. Artemisinins are the first-line antimalarial drugs. However, their therapeutic efficacy is significantly limited by poor solubility and short biological half-life. To overcome these limitations and enhance drug accumulation in , we developed a glucose-functionalized redox-responsive dihydroartemisinin (DHA) prodrug nanosystem (D@GLU-PMs-SS). The nanosystem was prepared by using DHA-dithiodipropionic acid-octadecylamine prodrug and D-α-Tocopherol polyethylene glycol 1000 succinate-arbutin conjugate. The resultant D@GLU-PMs-SS exhibited excellent stability under conditions of storage and physiological environment. D@GLU-PMs-SS could be activated by glutathione (GSH), leading to the dissociation of nanoparticles and subsequent release of free DHA. experiments revealed that the host erythrocyte uptake of glucose-functionalized nanoparticles was significantly enhanced GLUT-mediated transport. Cellular experiments illustrated that D@GLU-PMs-SS effectively reduced GSH concentrations in . Furthermore, D@GLU-PMs-SS displayed remarkable efficacy in inhibiting the growth of while maintaining biosafety. Overall, this study developed a strategy to enhance the targeting of nanoparticles to improve their therapeutic efficacy against malaria, warranting further investigation in clinical trials.
尽管疟疾已得到有效控制，但它仍然对全球健康构成威胁。青蒿素是一线抗疟药物。然而，它们的治疗效果因溶解度差和生物半衰期短而受到显著限制。为了克服这些限制并增强药物在体内的蓄积，我们开发了一种葡萄糖功能化的氧化还原响应型二氢青蒿素（DHA）前药纳米系统（D@GLU-PMs-SS）。该纳米系统是通过使用DHA-二硫代二丙酸-十八烷基胺前药和D-α-生育酚聚乙二醇1000琥珀酸酯-熊果苷共轭物制备的。所得的D@GLU-PMs-SS在储存和生理环境条件下表现出优异的稳定性。D@GLU-PMs-SS可被谷胱甘肽（GSH）激活，导致纳米颗粒解离并随后释放游离的DHA。实验表明，葡萄糖功能化纳米颗粒通过GLUT介导的转运显著增强了宿主红细胞摄取。细胞实验表明，D@GLU-PMs-SS有效降低了细胞内的GSH浓度。此外，D@GLU-PMs-SS在抑制疟原虫生长的同时保持生物安全性方面显示出显著疗效。总体而言，本研究开发了一种增强纳米颗粒靶向性的策略，以提高其抗疟治疗效果，值得在临床试验中进一步研究。
