Functionally engineered ‘hepato-liposomes’: Combating liver-stage malaria in a single prophylactic dose

Abstract Primaquine continues to remain the gold standard molecule with an incumbent toxicity profile, as far as radical treatment of malaria is concerned. Better molecules are available at experimental level but their targeted delivery is a challenge. The present work identifies ‘Decoquinate (DQN)’ as a repurposed, safer drug molecule with a potential to function as an appealing replacement for primaquine active against liver-stage malaria. The work focuses on delivering the highly lipophilic DQN (log P ∼ 5) in a liposomal carrier system to ‘sporozoite infested hepatocytes’ using two different in-house synthesized hepatotropic ligands. Functionally engineered ‘hepato-liposomes’ exhibit differences in their DQN loading capacities but no significant change in morphology or particle size and are also not affected by freeze drying. Two ligands, targeting different receptors on hepatocytes, have been compared for their in vitro and in vivo drug delivery efficiency in liver stage malaria. The studies reveal superior antimalarial efficacy of differently designed DQN loaded liposomes and demonstrate antimalarial efficacy at a low dose of 0.5 mg/kg for a repurposed molecule like DQN. The in vivo studies successfully discriminate the functional efficiency of the carriers and establish the importance of design in liposomal drug delivery for malarial prophylaxis.