Xavier Fernàndez Busquets’ joint IBEC-ISGlobal Nanomalaria group has moved a step closer to the validation of immunoliposomes as a vehicle for antimalarial drugs by showing that they increase the efficacy of lipohilic (poorly soluble) compounds in a mouse model of malaria.
The results, published in Biomaterials, suggest that this strategy could be used for the treatment of severe malaria.
Most antimalarial drugs currently in the pipeline are poorly soluble in water, and high amounts are needed to ensure their efficacy, particularly in cases of severe malaria.
Drug-loaded immunoliposomes enable rapid parasite clearance and could be used for severe malaria treatment
To address this, the Nanomalaria team have been developing nanovehicles that directly deliver the drug to parasite-infected red blood cells. In a previous study with ‘humanised’ mice, they showed that chloroquine encapsulated in nanovesicles covered with antibodies that target a red blood cell protein were more effective in clearing the parasite as compared to free drug. However, the WHO no longer recommends chloroquine therapy due to the widespread distribution of drug-resistant parasites.
In this study, the authors applied a similar technique with novel antimalarial drugs capable of overcoming resistance mechanisms: an amiquinoline and an aminoalcohol. They first validated a technique with high encapsulation yields and antibodies that allow specific targeting to red blood cells. They then showed that these immunoliposomes, when administered to mice infected with Plasmodium yoelli (which causes a disease similar to that found in humans), succeeded in decreasing blood parasitemia from severe to uncomplicated malaria densities. This was not the case for drug encapsulated in non-antibody covered liposomes.
“There is an urgent need to increase the repertoire of drugs to treat severe malaria,” explains Xavier. “The immunoliposomes described in this study represent an attractive strategy, since they rapidly clear parasites from infected red blood cells.”
The authors conclude that the immunoliposome half-life in blood needs to be increased while its erythrocyte agglutination effect should be reduced before the prototype presented in the study is used in the clinics.
Source article: Moles E, Galiano S, Gomes A, Quiliano M, Teixeira C, Aldana I, Gomes P, Fernàndez-Busquets X. (2017). ImmunoPEGliposomes for the targeted delivery of novel lipophilic drugs to red blood cells in a falciparum malaria murine model. Biomaterials, 145:178-191.