Department of Chemistry, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06099 Halle (Saale), Germany.
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06099 Halle (Saale), Germany.
Molecules. 2023 Jul 4;28(13):5208. doi: 10.3390/molecules28135208.
Malaria is one of the major life-threatening health problems worldwide. Artesunate is the most potent antimalarial drug to combat severe malaria. However, development of drug resistance, short plasma half-life, and poor bioavailability limit the efficacy of this drug. Here, we applied the dimerization concept to synthesize dimeric artesunate glycerol monocaprylate conjugate (D-AS-GC) by conjugating artesunate (AS) with glycerol monocaprylate (GC) via esterification reaction. D-AS-GC conjugate, AS, and GC were well characterized by H NMR, attached proton test (APT) C NMR and 2D NMR spectroscopy. D-AS-GC conjugate was further analyzed by ESI-TOF MS. Finally, a series of nanoemulsion preconcentrate (F1-F6) of D-AS-GC was prepared by mixing different ratios of oil and surfactant/cosurfactant and evaluated after dilution with an aqueous phase. The optimized formulation (F6) exhibits a clear nanoemulsion and the hydrodynamic diameter of the dispersed phase was determined by DLS and DOSY NMR spectroscopy. The morphology of the nanoemulsion droplets of F6 was investigated by AFM, which revealed the formation of tiny nanoemulsion droplets on a hydrophilic mica substrate. Moreover, using a less polar silicon wafer led to the formation of larger droplets with a spherical core shell-like structure. Overall, the rational design of the dimeric artesunate-based nanoemulsion preconcentrate could potentially be used in more efficient drug delivery systems.
疟疾是全球范围内威胁生命的主要健康问题之一。青蒿琥酯是治疗重症疟疾最有效的抗疟药物。然而，耐药性的发展、血浆半衰期短和生物利用度差限制了该药物的疗效。在这里，我们应用二聚化概念通过酯化反应将青蒿琥酯（AS）与甘油单辛酸酯（GC）偶联合成二聚青蒿琥酯甘油单辛酸酯缀合物（D-AS-GC）。通过 1 H NMR、连接质子测试（APT）C NMR 和 2D NMR 光谱对 D-AS-GC 缀合物、AS 和 GC 进行了很好的表征。通过 ESI-TOF MS 进一步分析 D-AS-GC 缀合物。最后，通过混合不同比例的油和表面活性剂/助表面活性剂制备了一系列 D-AS-GC 的纳米乳预浓缩物（F1-F6），并在用水相稀释后进行评估。优化的配方（F6）表现出明显的纳米乳液，通过 DLS 和 DOSY NMR 光谱确定分散相的水动力直径。通过 AFM 研究了 F6 的纳米乳液液滴的形态，结果表明在亲水云母基底上形成了微小的纳米乳液液滴。此外，使用极性较小的硅片导致形成具有球形核壳结构的较大液滴。总的来说，基于二聚青蒿琥酯的纳米乳预浓缩物的合理设计可能会被用于更有效的药物传递系统。
