Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium

Control of Malaria by Bio-Therapeutics and Drug Delivery Systems

“…This results in a versatile structure in which hydrophilic drugs can be encapsulated in the inner aqueous core while hydrophobic agents will be embedded in the lipid bilayer structure [49]. Several research groups have investigated the use of liposomal formulations for the delivery of different antimalarial Chloroquine PEGylated poly-L -lysine-based dendrimers To induce controlled and sustained delivery [142] Chloroquine PEGylated neutral and cationic liposomes Treatment of chloroquine resistant malaria parasites [143] Chloroquine Amidated pectin hydrogel beads Delay the release of oral chloroquine to distal parts of the gastrointestinal tract [144] Chloroquine and Primaquine Dendritic derivatives Reduce the toxicity of the used anti-malarial drugs [145] Chloroquine Poly (amidoamines) drug conjugates Selectively deliver chloroquine to Plasmodium-infected red blood cells [146] Monensin Liposomes Improving the anti-malarial activity of monensin [147] Chloroquine (CQ) is an effective anti-malarial drug against all five species of parasites. The activity of CQ is thought to take place in the parasite's acidic digestive vacuole (DV) against the intraerythrocytic stage of the human malaria parasite [51].…”

“…This sdAb binds favourably to an area that is slightly overlapping with the MyoA binding groove, and impedes MyoA binding by MTIP. Antibodies have been thoroughly investigated in targeting specific malarial antigens and antimalarial drugs for both therapeutic [131][132][133][134][135][136][137] and diagnostic [138][139][140][141][142][143][144][145][146][147][148] purposes. Moreover, antibodies possess high potential to deliver anti-malarial drugs directly to parasites, thus reducing the risk of adverse drug reactions.…”

Novel strategies for Plasmodium-targeted drug delivery

“…[10] Finally, some PAAs have been shown to possess significant antiplasmodial activity in themselves, which is most likely based on the inhibition of RBC invasion due to the masking of necessary cell interactions by the polymer binding to parasite surfaces. [8] 2.3. Carrier, targeting, drug, plus prophylactic activities…”

“…[12] Experimental evidence has shown that malaria parasites are targeted by different PAAs, which in turn bind plasmodia from widely diverging malarias. [8] Because the antiparasitic mechanism of these polymers seems to operate through inhibition of Plasmodium invasion of RBCs, the failure of egressed parasites to quickly invade a new host cell will expose the pathogen to the immune system for a longer time. Perhaps PAA-based treatments can be developed as a new vaccination concept that requires the existence of an active malaria infection at the time of administration.…”

Polyamidoamine Nanoparticles as Nanocarriers for the Drug Delivery to Malaria Parasite Stages in the Mosquito Vector

“…The PAA structures AGMA1, ISA1 and ISA23 (Figure 3) have been explored for the encapsulation and targeted delivery of the antimalarial drugs chloroquine and primaquine [70]. AGMA1 is obtained by polyaddition of 4-aminobutylguanidine (agmatine) with 2,2-bis(acrylamido)acetic acid and contains tert-amine, carboxyl and guanidine groups.…”