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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Nanomedicine-Nanotechnology Biology and Medicine; v. 22, NOV 2019.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 16/19145-7 - Uso de lipossomos e RNA autorreplicativo como vacina contra antígeno PfRH5 de Plasmodium falciparum e desenvolvimento de técnicas para lipossomos direcionáveis
• Beneficiário: Wesley Luzetti Fotoran
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/24267-7 - Papel de modificadores de cromatina na dinâmica da transcrição de fatores de virulência no parasita da Malária Plasmodium falciparum
• Beneficiário: Gerhard Wunderlich
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/08626-7 - Estabelecimento de técnicas de vacina de RNA fazendo uso de RNA autorreplicativo estabilizado por lipossomos catiônicos in vitro e in vivo
• Beneficiário: Nicole Kleiber
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/17174-7 - Avaliação de fatores que influem na expressão de famílias multigênicas var, rif e surf de P. falciparum, o parasita da malária humana
• Beneficiário: Gerhard Wunderlich
• Modalidade de apoio: Auxílio à Pesquisa - Regular