The lipid self-emulsifying system has been advanced as a promising delivery vehicle for improving the solubility and bioavailability of artemether and lumefantrine. However, the observed kinetic instability (propensity of lumefantrine to rapid crystallisation from nano-scale droplets) in aqueous acid has impelled some researchers to incorporate surfactants/solubilizers in the dissolution medium prior to dissolution studies. Thus, in our present work, we sought to prepare micro/large nano-scale (> 100 nm) and yet kinetically stable lumefantrine lipid self-emulsifying system (that would not require an external drug dissolution enhancing agent in the dissolution medium) and palm kernel oil-based 100 nm kinetically stable artemether lipid self-emulsifying system with rapid emulsification time. COVID-19 and Plasmodium falciparum-infected Africans with previous long exposure to malaria have manifested attenuated inflammatory cytokines more than malaria-naive patients. Therefore, the ingestion of artemether-lumefantrine with enhanced solubility may further promote blunting of cytokines. Therefore, this work was aimed at preparing (< 100 nm) stable artemether and aqueous acid-stable micro/large nano-scale (> 100 nm) lumefantrine lipid self-emulsifying system destined for improved antimalarial and anti-inflammatory activities. The droplet sizes of all the liquid artemether and lumefantrine formulations were between 8.95–39.88 and 1018–4195 nm, respectively. The loading efficiency for all the formulations was, between 72.91 ± 2.89 and 100.00 ± 0.29%. All the artemether and lumefantrine batches emulsified within the range of 3.90 ± 0.69 to 12.26 ± 0.69 s. Stable and transparent emulsions were formed on aqueous dilution to 1000 ml. The percentage drug released for artemether and lumefantrine ranged from 76.25 ± 2.98 to 99.22 ± 1.61%. The solid lipid self-emulsifying systems produced, had fair and passable flow properties. Differential scanning calorimetry revealed that the solid artemether and lumefantrine lipid self-emulsifying system were amorphous. Solidification with Neusilin FH2 or surfactant replacement with Kolliphor EL and Kollidon VA 64 fine prevented micro-or large nano-scale lumefantrine lipid self-emulsifying system from crystallisation in aqueous acid (pH 1.2). Higher antimalarial activity and remarkable anti-inflammatory effects (P < 0.05) favoured the lipid self-emulsifying formulations. Optimal in vitro and in vivo results (enhanced antimalarial and anti-inflammatory activities) were obtained with kinetically stable lumefantrine micro/large nano-scale droplets and kinetically stable palm kernel oil-based (< 50 nm) artemether lipid self-emulsifying system droplets.

中文翻译：

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提高蒿甲醚和苯芴醇的溶解度的脂质载体，有望用于治疗诱发的疟疾和炎症：体外和体内评估

脂质自乳化系统已发展成为一种有前景的递送载体，可提高蒿甲醚和苯芴醇的溶解度和生物利用度。然而，在酸水溶液中观察到的动力学不稳定性（苯芴醇从纳米级液滴快速结晶的倾向）促使一些研究人员在溶出研究之前在溶出介质中加入表面活性剂/增溶剂。因此，在我们目前的工作中，我们试图制备微/大纳米级（> 100 nm）且动力学稳定的苯芴醇脂质自乳化系统（不需要在溶出介质中添加外部药物溶出增强剂）和棕榈油基于仁油的 100 nm 动力学稳定的蒿甲醚脂质自乳化系统，具有快速乳化时间。先前长期接触疟疾的感染了 COVID-19 和恶性疟原虫的非洲人比未患疟疾的患者表现出更弱的炎症细胞因子。因此，摄入具有增强溶解度的蒿甲醚-本芴醇可能会进一步促进细胞因子的钝化。因此，本工作旨在制备（< 100 nm）稳定的蒿甲醚和水酸稳定的微/大纳米级（> 100 nm）苯芴醇脂质自乳化系统，以提高抗疟和抗炎活性。所有液体蒿甲醚和本芴醇制剂的液滴尺寸分别在8.95-39.88和1018-4195 nm之间。所有配方的负载效率在 72.91 ± 2.89 和 100.00 ± 0.29% 之间。所有批次的蒿甲醚和苯芴醇均在 3.90 ± 0.69 至 12.26 ± 0.69 s 范围内乳化。用水稀释至1000ml时形成稳定且透明的乳液。蒿甲醚和苯芴醇的释放药物百分比范围为 76.25 ± 2.98 至 99.22 ± 1.61%。所产生的固体脂质自乳化体系具有良好且合格的流动特性。差示扫描量热法显示固体蒿甲醚和本芴醇脂质自乳化体系呈无定形。用 Neusilin FH2 进行固化或用 Kolliphor EL 和 Kollidon VA 64 Fine 替代表面活性剂可防止微米级或大型纳米级苯芴醇脂质自乳化系统在酸水溶液（pH 1.2）中结晶。脂质自乳化制剂具有较高的抗疟活性和显着的抗炎作用（P < 0.05）。使用动力学稳定的本芴醇微/大纳米级液滴和动力学稳定的棕榈仁油基（< 50 nm）蒿甲醚脂质自乳化系统液滴获得了最佳的体外和体内结果（增强的抗疟和抗炎活性）。