Cetirizine and liposomal Inhibitory Effect on Plasmodium berghei P-Glycoproteins and Chloroquine Induced Pruritus

Abstract

Chloroquine was the mainstay of malaria chemotherapy in the world for decades but lost its efficacy against resistant strains of Plasmodium and also individual discontinuation of therapy due to associated chloroquine-induced pruritic side effects. This increasing resistance by Plasmodium parasite against antimalarial drugs led to the search for new antimalarial drugs with cost-effective approach. The interaction of chloroquine with cetirizine as chloroquine resistance modulator was examined and also the drugs were encapsulated in liposome for co-delivery in enhancing antimalarial activity. The drugs were encapsulated in liposomal vesicle by active loading technique (ion trapping method).

In vivo model study was carried out to evaluate the antimalarial activities against chloroquine resistance strains of P. berghei (ANKA) and antipruritic effects against chloroquine-induced pruritus. Cetirizine proved to either possess intrinsic anti-malarial activity or restoring the activity of chloroquine against the Plasmodium resistance strain by binding competitively to parasite p-glycoproteins to inhibit chloroquine efflux. Cetirizine as H1 tricyclic anti-histamine have the tendency of binding to the alkyl amino side chain of chloroquine to increase its lipophilicity and prevent efflux. Cetirizine and liposome had shown to be protective against Plasmodium parasites induced anaemia, hepatocytes loss and inflammation, and chloroquine-induced pruritus when used together with chloroquine in treatment of malaria. Liposome nanoparticle drug delivery vesicle proved to be effective as site targeting dosage form and addition of stealth (PEG) improved tissues penetration.

This investigation proved cetirizine as an adjunct in modifying the efficacy of chloroquine as a first line antimalarial drug in use and in pregnancy. This combination was seen to be protective against Plasmodium parasites induced anaemia, chloroquine-induced pruritus and can be promising in resolving cerebral malaria of severe P. falciparum complication with more benefit achieved in a liposomal vesicle.