Immunoliposome-mediated drug delivery to Plasmodium-infected and non-infected red blood cells as a dual therapeutic/prophylactic antimalarial strategy.

摘要: One of the most important factors behind resistance evolution in malaria is failure to deliver sufficiently high amounts drugs early stages Plasmodium-infected red blood cells (pRBCs). Despite having been considered for decades as a promising approach, delivery antimalarials encapsulated immunoliposomes targeted pRBCs has not progressed towards clinical applications, whereas vitro assays rarely reach drug efficacy improvements above 10-fold. Here we show that encapsulation efficiencies reaching >96% are achieved weak basic chloroquine (CQ) and primaquine using pH gradient loading method liposomes containing neutral saturated phospholipids. Targeting antibodies best conjugated through their primary amino groups, adjusting chemical crosslinker concentration retain significant antigen recognition. Antigens from non-parasitized RBCs have also targets cell affecting erythrocytic metabolism. Using this strategy, unprecedented complete nanocarrier targeting intraerythrocytic parasite which there lack specific extracellular molecular tags. Immunoliposomes studded with monoclonal raised against erythrocyte surface protein glycophorin A were capable 100% at low 0.5μM total lipid culture, >95% added retained on surfaces. When exposed only 15min Plasmodium falciparum cultures stages, free CQ had no effect viability up 200nM, immunoliposomal 50nM completely arrested its growth. In vivo mice showed cleared pathogen below detectable levels dose 0.5mg/kg, administered 1.75mg/kg was, most, 40-fold less efficient. Our data suggest improvement part due prophylactic found by host right very moment invasion.