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

Author(s)

Fotoran, Wesley L. ^[1] ; Muentefering, Thomas ^[2] ; Kleiber, Nicole ^[1] ; Miranda, Beatriz N. M. ^[3] ; Liebau, Eva ^[2] ; Irvine, Darrell J. ^{[4, 5, 6, 7]} ; Wunderlich, Gerhard ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, SP - Brazil

^[2] Westfalische Wilhelms Univ Munster, Inst Anim Physiol, Dept Mol Physiol, Munster - Germany

^[3] Inst Technol Res IPT, Sao Paulo, SP - Brazil

^[4] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 - USA

^[5] Howard Hughes Med Inst, Chevy Chase, MD - USA

^[6] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[7] MIT & Harvard, Ragon Inst MGH, Cambridge, MA - USA

• Document type: Journal article
• Source: Nanomedicine-Nanotechnology Biology and Medicine; v. 22, NOV 2019.
• Web of Science Citations: 3

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. (C) 2019 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 16/19145-7 - Application of liposomes for RNA vaccines against the Plasmodium falciparum PfHR5 antigen and establishment of a technical approach for guided liposomes
• Grantee: Wesley Luzetti Fotoran
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/24267-7 - Role of chromatin modifiers in the transcription dynamics of virulence factors of the human malaria parasite Plasmodium falciparum
• Grantee: Gerhard Wunderlich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/08626-7 - Establishment of RNA vaccine techniques using RNA replicons stabilized by cationic liposomes in vitro and in vivo
• Grantee: Nicole Kleiber
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/17174-7 - Factors influencing expression of variant antigen families var, rif and surf of Plasmodium falciparum, the human malaria parasite
• Grantee: Gerhard Wunderlich
• Support Opportunities: Regular Research Grants