Table 6.

Prodrug-based nanocarriers for malaria

Drug	Formulation	Prodrug	Target	Advantages	References
Endochin-like quinolones (ELQ-300)	–	Alkoxycarbonate ester prodrugs of ELQ-300	Cytochrome bc1 complex	Promising prodrug with enhanced physicochemical and metabolic properties and better potential for the clinical formulation	[60]
Artesunate	Liposomes	Dimeric artesunate phospholipid (Di-ART-GPC)	Parasitic mitochondria	Longer retention time in blood improved pharmacokinetic profile and enhanced uptake by infected RBCs. Enhanced parasite clearance tested in P. berghei–infected mice in vivo and enhanced survival as compared with free drug.	[33]
Artesunate (ART)	Nanocapsule	Artesunate-heparin conjugate (ART-HEP)	Parasitic mitochondria	Specifically, the target to iRBCs and ART-HEP-NCPs exhibits higher ART loading and enhanced half-life	[19]
3,5-Diaryl-2-aminopyrazine sulfone	–	3,5-Diaryl-2-aminopyrazine sulfoxide	Phosphatidylinositol 4-kinase (PI4K)	Prodrug did not improve in vivo efficacy but improved drug exposure with oral dosing and longer half-life is achieved.	[60]
bis-N-Alkylamidines		Amidoxime derivatives as a prodrug	Choline	Amidoxime prodrug significantly improves oral antimalarial activity.	[61]