Last Updated: 17/09/2024
Study on regulating glutathione content with the help of thermal sponge nanocarriers to inhibit artemisinin resistance
Objectives
*The title and abstract were machine translated from Mandarin
In the project, a targeted intra-erythrocytic drug delivery system will be constructed to dexterously co-encapsulate artemisinin and D,L-buthionine-(S,R)sulphoximine (BSO) by using a thermosponge nanocarrier.
The discovery of artemisinin is a milestone in the history of malaria treatment, artemisinin-based combination therapies (ACTs) have become the first-line treatments for uncomplicated falciparum malaria. However, access to ACTs is still limited in most malaria-endemic countries and the therapy efficacy has declined, inducing antimalarial-drug resistance. It is reported that the altered glutathione (GSH) levels have remarkable impact on artemisinin resistance. Artemisinin-resisitant parasites could be using GSH to reduce the pro-oxidant effects of artemisinin, and supplyling GSH to the host erythrocyte to ensure its integrity and survival, resulting in an increase of tolerance to the drug. Thus, the proposal states that using DL-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS) to inhibit GSH synthesis maybe revert artemisinin resistance. The therapy efficacies were evaluated by determining the GSH levels, antimalarial activity and recrudescence rate in plasmodium-infected erythrocytes and mice. The results will pave the way for preventing artemisinin antimalarials resistance and provide inspirations for designing combined antimalarial drugs delivery system.
Jan 2019 — Dec 2021
$29,901
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