UNASSIGNED: One of the most important factors behind resistance evolution in @entity311 is the failure to deliver sufficiently high amounts of drugs to early stages of @entity3964 -infected red blood cells (pRBCs). Despite having been considered for decades as a promising approach, the delivery of antimalarials encapsulated in immunoliposomes targeted to pRBCs has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here we show that encapsulation efficiencies reaching >96% are achieved for the weak basic drugs @entity503 (CQ) and primaquine using the pH gradient loading method in liposomes containing neutral saturated phospholipids. Targeting antibodies are best conjugated through their primary @entity1472 groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the delivery to the cell of drugs not affecting the erythrocytic metabolism. Using this strategy, we have achieved unprecedented complete nanocarrier targeting to early intraerythrocytic stages of the @entity311 parasite for which there is a lack of specific extracellular molecular tags. Immunoliposomes studded with monoclonal antibodies raised against the erythrocyte surface protein glycophorin A were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 M total lipid in the culture, with >95% of added liposomes retained on cell surfaces. When exposed for only 15min to @entity3964 in vitro cultures of early stages, free CQ had no significant effect on the viability of the parasite up to 200nM, whereas immunoliposomal 50nM CQ completely arrested its growth. In vivo assays in @entity19 showed that immunoliposomes cleared the pathogen below detectable levels at a CQ dose of 0.5mg/kg, whereas free CQ administered at 1.75mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

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

@entity1472 :: ('CHEBI:46882', 'Chemical') :: ['amino'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity3964 :: ('5833', 'Species') :: ['Plasmodium falciparum', 'Plasmodium'] @entity311 :: ('MESH:D008288', 'Disease') :: ['malaria'] @entity503 :: ('MESH:D002738', 'Chemical') :: ['chloroquine']
@entity3964 :: (5833,Species) :: ['Plasmodium']
