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A multilamellar nanoliposome stabilized by interlayer hydrogen bonds increases antimalarial drug efficacy
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 5.570 ) Pub Date : 2019-10-21 , DOI: 10.1016/j.nano.2019.102099
Wesley L. Fotoran, Thomas Müntefering, Nicole Kleiber, Beatriz N.M. Miranda, Eva Liebau, Darrell J. Irvine, Gerhard Wunderlich

Lipid particles for drug delivery can be modified to create multilayer vesicles with higher stability and improved cargo interaction. Here, we used lipids capable of forming hydrogen bonds instead of covalent bonds and designed stable vesicles-inside-vesicles with a high capacity of entrapping antimalarial drugs such as chloroquine (hydrophilic) and Artemisinin (lipophilic). In vitro treatment of the drug-sensitive P. falciparum strain NF54 showed that encapsulated drugs resulted in 72% and 60% lower IC50 values for each drug, respectively. Fluorochrome-labeling of a cargo-peptide or of membrane-resident lipids indicated that vesicles interacted more specifically with parasite-infected erythrocytes than with normal red blood cells. Accordingly, vesicle-confined chloroquine was able to elicit a stronger antiparasitic effect than free chloroquine in a lethal murine model of infection. Being permissive not only to small molecules but also to larger peptides, hydrogen-bond linked multilamellar liposomes are a very promising approach for enhanced drug delivery.
更新日期:2019-10-22

 

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