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

ABSTRACT: 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.

SUBMITTER: Tian Y

PROVIDER: S-EPMC9258070 | biostudies-literature |

REPOSITORIES: biostudies-literature

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