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

Wesley L Fotoran; Thomas Müntefering; Nicole Kleiber; Beatriz N M Miranda; Eva Liebau; Darrell J Irvine; Gerhard Wunderlich

doi:10.1016/j.nano.2019.102099

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

Nanomedicine. 2019 Nov:22:102099. doi: 10.1016/j.nano.2019.102099. Epub 2019 Oct 21.

Authors

Wesley L Fotoran¹, Thomas Müntefering², Nicole Kleiber¹, Beatriz N M Miranda³, Eva Liebau², Darrell J Irvine⁴, Gerhard Wunderlich⁵

Affiliations

¹ Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
² Department of Molecular Physiology, Institute of Animal Physiology, Westfälische Wilhelms University of Münster, Münster, Germany.
³ Institute for Technological Research (IPT), Cid. Universitária-Butantã, São Paulo, Brazil.
⁴ 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.
⁵ Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: wundergerd@gmail.com.

PMID: 31648039
DOI: 10.1016/j.nano.2019.102099

Abstract

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.

Keywords: Drug delivery; Hydrogen bonds; Multilamellar liposomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / administration & dosage
Antimalarials / pharmacology*
Antimalarials / therapeutic use
Artemisinins / pharmacology
Chloroquine / pharmacology
Cross-Linking Reagents / chemistry
Drug Delivery Systems
Hydrogen Bonding
Liposomes
Malaria, Falciparum / drug therapy
Mice, Inbred BALB C
Mice, Inbred C57BL
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Particle Size
Plasmodium falciparum / drug effects
Treatment Outcome

Substances

Antimalarials
Artemisinins
Cross-Linking Reagents
Liposomes
Chloroquine
artemisinin