Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria

• Published in: Journal of nanobiotechnology Vol. 20; no. 1; pp. 318 - 22
• Main Authors: Tian, Ya, Zheng, Zhongyuan, Wang, Xi, Liu, Shuzhi, Gu, Liwei, Mu, Jing, Zheng, Xiaojun, Li, Yujie, Shen, Shuo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06-07-2022; BioMed Central; BMC
• Subjects: Animals; Artemisinin; Bilayers; Blood Brain Barrier; Brain diseases; Brain-targeted liposomes; Carrier proteins; Central nervous system diseases; Cerebral malaria; Chemical properties; Cholesterol; Conjugates; Dextrose; Drug delivery systems; Drug therapy; Drugs; Fluorescence; Glucose; Glucose - chemistry; Glucose transporter; Glucose Transporter Type 1; GLUT1; Health aspects; Intranasal administration; Laboratory animals; Liposomes; Liposomes - chemistry; Malaria; Malaria, Cerebral - drug therapy; Mice; Molecular dynamics; Nanocomposites; Nanoparticles; Neurological complications; Pharmaceutical research; Pharmaceuticals; Pharmacokinetics; Phospholipids; Plasmodium falciparum; Potash; Potassium; Production processes; Simulation; Vector-borne diseases; Vehicles; China; Beijing China; United States > US; Germany; Cerebral malaria; Molecular dynamics; GLUT1; Blood Brain Barrier; Brain-targeted liposomes
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01493-8

Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood-brain barrier as a target for a synthesized cholesterol-undecanoic acid-glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria.