Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy
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 dr...
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Elsevier
2025-12-01
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| Series: | International Journal of Pharmaceutics: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156725000556 |
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| author | Rongrong Wang Jiaqi Yang Jihong Qiang Qingxia Li Geng Wang Canqi Ping Kesheng Liu Ruili Wang Bin Zheng Guolian Ren Shuqiu Zhang |
| author_facet | Rongrong Wang Jiaqi Yang Jihong Qiang Qingxia Li Geng Wang Canqi Ping Kesheng Liu Ruili Wang Bin Zheng Guolian Ren Shuqiu Zhang |
| author_sort | Rongrong Wang |
| collection | DOAJ |
| description | 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 Plasmodium, 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. In vitro experiments revealed that the host erythrocyte uptake of glucose-functionalized nanoparticles was significantly enhanced via GLUT-mediated transport. Cellular experiments illustrated that D@GLU-PMs-SS effectively reduced GSH concentrations in Plasmodium. Furthermore, D@GLU-PMs-SS displayed remarkable efficacy in inhibiting the growth of Plasmodium 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. |
| format | Article |
| id | doaj-art-8d6904386a194778a9b5d0637db3c993 |
| institution | DOAJ |
| issn | 2590-1567 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj-art-8d6904386a194778a9b5d0637db3c9932025-08-20T02:56:20ZengElsevierInternational Journal of Pharmaceutics: X2590-15672025-12-011010037010.1016/j.ijpx.2025.100370Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapyRongrong Wang0Jiaqi Yang1Jihong Qiang2Qingxia Li3Geng Wang4Canqi Ping5Kesheng Liu6Ruili Wang7Bin Zheng8Guolian Ren9Shuqiu Zhang10School 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; Third Hospital of Shanxi Medical University, Taiyuan 030032, China; Corresponding authors at: School of Pharmacy, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China.School of Pharmacy, Shanxi Medical University, Taiyuan 030001, ChinaSchool of Pharmacy, Shanxi Medical University, Taiyuan 030001, ChinaSchool of Pharmacy, Shanxi Medical University, Taiyuan 030001, ChinaSchool of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, ChinaSchool of Pharmacy, Shanxi Medical University, Taiyuan 030001, ChinaSchool of Pharmacy, Shanxi Medical University, Taiyuan 030001, ChinaSchool 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, ChinaSchool 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, ChinaSchool 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, ChinaSchool 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; Corresponding authors at: School of Pharmacy, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China.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 Plasmodium, 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. In vitro experiments revealed that the host erythrocyte uptake of glucose-functionalized nanoparticles was significantly enhanced via GLUT-mediated transport. Cellular experiments illustrated that D@GLU-PMs-SS effectively reduced GSH concentrations in Plasmodium. Furthermore, D@GLU-PMs-SS displayed remarkable efficacy in inhibiting the growth of Plasmodium 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.http://www.sciencedirect.com/science/article/pii/S2590156725000556DihydroartemisininMalariaRedox-responsive prodrug nanoparticlesGlucose-targeted drug delivery |
| spellingShingle | Rongrong Wang Jiaqi Yang Jihong Qiang Qingxia Li Geng Wang Canqi Ping Kesheng Liu Ruili Wang Bin Zheng Guolian Ren Shuqiu Zhang Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy International Journal of Pharmaceutics: X Dihydroartemisinin Malaria Redox-responsive prodrug nanoparticles Glucose-targeted drug delivery |
| title | Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy |
| title_full | Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy |
| title_fullStr | Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy |
| title_full_unstemmed | Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy |
| title_short | Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy |
| title_sort | glucose functionalized redox responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy |
| topic | Dihydroartemisinin Malaria Redox-responsive prodrug nanoparticles Glucose-targeted drug delivery |
| url | http://www.sciencedirect.com/science/article/pii/S2590156725000556 |
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