A multilamellar nanoliposome stabilized by interlayer hydrogen bonds increases antimalarial drug efficacy.

Autor: Fotoran WL; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Müntefering T; Department of Molecular Physiology, Institute of Animal Physiology, Westfälische Wilhelms University of Münster, Münster, Germany., Kleiber N; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Miranda BNM; Institute for Technological Research (IPT), Cid. Universitária-Butantã, São Paulo, Brazil., Liebau E; Department of Molecular Physiology, Institute of Animal Physiology, Westfälische Wilhelms University of Münster, Münster, Germany., Irvine DJ; Department of Biological Engineering and Department of Materials Science and Engineering, MIT, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Wunderlich G; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: wundergerd@gmail.com.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2019 Nov; Vol. 22, pp. 102099. Date of Electronic Publication: 2019 Oct 21.
DOI: 10.1016/j.nano.2019.102099
Abstrakt: 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 IC 50 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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE