New malaria strategy proposes using unaffected red blood cells as drug carriers

IBEC and ISGlobal’s joint unit, Nanomalaria, has published a new therapeutic strategy against malaria.

The study, which appeared in the current edition of the Journal of Controlled Release, tackles a major hurdle in malaria treatments, which is that most antimalarial drugs start working on the infected cell quite late in Plasmodium’s life cycle, when their effect is often too short to be lethal to the parasite. The work has been done in collaboration with GlaxoSmithKline, as one of the few cases of partnerships involving industry in the research and development of innovative antimalarial nanomedicines.

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The new strategy proposes using unaffected red blood cells (RBCs) as drug carriers, thereby ensuring that the parasite doesn’t even get the chance to start its development cycle, which it normally does during a ‘recovery period’ after a quick and stealthy entry into an RBC. “Previous strategies have always considered infected cells as the target,” says Xavier Fernàndez-Busquets, head of the Nanomalaria joint group. “By using unaffected cells, we’re pre-empting infection by Plasmodium by making sure that when it tries to find a cell in which to settle and develop, the drug is already there.”

Image: Representation of immunoliposome models encapsulating an amphiphilic weak basic drug and functionalized with antibodies linked through four different conjugation strategies, all based on the formation of a thioether bond between a thiolated antibody and a maleimide-conjugated lipid.

Using unaffected RBCs has several other advantages. RBCs are biocompatible, and natural mechanisms already exist for their safe elimination from the body, unlike other introduced nanocarriers. They also have a long life span, which means drug circulation is prolonged.

Of course, this strategy could only be used for drugs known to have no effect on the metabolism of RBCs, but Xavier is confident that such antimalarials will be developed in the future. “If the pathogen can encounter its enemy at home, right at the very moment of entering the cell, this could significantly reduce its capacity for survival,” he concludes.

Reference article: Moles E, Urbán P, Jiménez-Díaz MB, Viera-Morilla S, Angulo-Barturen I, Busquets MA, Fernàndez-Busquets X. (2015). Immunoliposome-mediated drug delivery to Plasmodium-infected and non-infected red blood cells as a dual therapeutic/prophylactic antimalarial strategy. J Control Release, 210, 217-229