The interstitial space, a widespread fluid-filled compartment throughout the body, is related to many pathophysiological alterations and diseases, attracting increasing attention. The vital role of interstitial space in malaria infection and treatment has been neglected current research efforts. We confirmed the reinfection capacity of parasites sequestrated in interstitial space, which replenish the mechanism of recurrence. Malaria parasite-infected mice were treated with artemisinin-loaded liposomes through the interstitial space and exhibited a better therapeutic response. Notably, compared with oral administration, interstitial administration showed an unexpectedly high activation and recruitment of immune cells, and resulted in better clearance of sequestered parasites from organs, and enhanced pathological recovery. The interstitial route of administration prolongs the blood circulation time of artemisinin and increases its plasma concentration, and may compensate for the inefficiency of oral administration and the nanotoxicity of intravenous administration, providing a potential strategy for infectious disease therapy.

间质空间是全身广泛的充满液体的隔间，与许多病理生理改变和疾病有关，引起了越来越多的关注。目前的研究工作忽视了间质空间在疟疾感染和治疗中的重要作用。我们证实了隔离在间质空间中的寄生虫的再感染能力，这补充了复发的机制。疟疾寄生虫感染的小鼠通过间质空间用载有青蒿素的脂质体进行治疗，并表现出更好的治疗反应。值得注意的是，与口服给药相比，间质给药显示出出乎意料的高免疫细胞活化和募集，并导致更好地清除器官中隔离的寄生虫，并增强病理恢复。