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Open AccessArticle

An ImmunoPEGliposome for Targeted Antimalarial Combination Therapy at the Nanoscale

1
Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain
2
Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, ES-08028 Barcelona, Spain
3
Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Martí i Franquès 1, ES-08028 Barcelona, Spain
4
Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, PO Box 81, Randwick, NSW 2031, Australia
5
School of Women’s and Children’s Health, UNSW Sydney, Sydney, NSW 2052, Australia
6
Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Avda. Diagonal 643, ES-08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(7), 341; https://doi.org/10.3390/pharmaceutics11070341
Received: 3 June 2019 / Revised: 27 June 2019 / Accepted: 11 July 2019 / Published: 16 July 2019
(This article belongs to the Special Issue From Drug Carriers to Vaccine Adjuvants in Malaria)
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PDF [18581 KB, uploaded 16 July 2019]
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Abstract

Combination therapies, where two drugs acting through different mechanisms are administered simultaneously, are one of the most efficient approaches currently used to treat malaria infections. However, the different pharmacokinetic profiles often exhibited by the combined drugs tend to decrease treatment efficacy as the compounds are usually eliminated from the circulation at different rates. To circumvent this obstacle, we have engineered an immunoliposomal nanovector encapsulating hydrophilic and lipophilic compounds in its lumen and lipid bilayer, respectively. The antimalarial domiphen bromide has been encapsulated in the liposome membrane with good efficiency, although its high IC50 of ca. 1 µM for living parasites complicates its use as immunoliposomal therapy due to erythrocyte agglutination. The conjugation of antibodies against glycophorin A targeted the nanocarriers to Plasmodium-infected red blood cells and to gametocytes, the sole malaria parasite stage responsible for the transmission from the human to the mosquito vector. The antimalarials pyronaridine and atovaquone, which block the development of gametocytes, have been co-encapsulated in glycophorin A-targeted immunoliposomes. The co-immunoliposomized drugs have activities significantly higher than their free forms when tested in in vitro Plasmodium falciparum cultures: Pyronaridine and atovaquone concentrations that, when encapsulated in immunoliposomes, resulted in a 50% inhibition of parasite growth had no effect on the viability of the pathogen when used as free drugs. View Full-Text
Keywords: combination therapy; immunoliposomes; malaria; nanomedicine; nanotechnology; Plasmodium; targeted drug delivery combination therapy; immunoliposomes; malaria; nanomedicine; nanotechnology; Plasmodium; targeted drug delivery
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Biosca, A.; Dirscherl, L.; Moles, E.; Imperial, S.; Fernàndez-Busquets, X. An ImmunoPEGliposome for Targeted Antimalarial Combination Therapy at the Nanoscale. Pharmaceutics 2019, 11, 341.

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