Comprehensive evaluation of chloroquine-resin complexes: functional, biopharmaceutical and antimalarial performance

Malaria remains a major global health burden, especially in children under the age of five. Pediatric treatment often requires tablet fragmentation for its dose adjustment according to body weight, which intensifies bitterness and may reduce treatment adherence. Complexation of bitter-tasting drugs with ion-exchange resins for taste masking is a promising strategy to improve palatability. Here, we evaluated whether a chloroquine-resin complex (CLQ-R) preserves the pharmacokinetic profile and antimalarial efficacy of chloroquine diphosphate (CLQ) while masking its bitter taste. CLQ-R was prepared at a 1:1 (w/w) drug-to-resin ratio using polacrilin potassium (Amberlite IRP88). The in vitro antimalarial activity of CLQ-R was assessed using Plasmodium falciparum 3D7 strain, and the parasite proliferation was determined by SYBR Green DNA-staining. CLQ plasma concentrations and mice biochemical parameters were evaluated following oral administration of CLQ or CLQ-R. The in vivo antimalarial activity was evaluated in P. berghei ANKA-infected C57BL/6 mice using the four-day suppressive and recrudescence tests, with parasitemia assessed by flow cytometry. Taste perception was determined by 48-hour two-bottle preference test. CLQ-R displayed similar plasma concentration and biochemical profiles to CLQ. CLQ-R was able to maintain a strong in vitro antimalarial activity with IC₅₀ of 30 nM with minimal hemolytic activity and reduced in vivo parasitemia by > 95%. Notably, mice exhibited a 15.5% higher preference for CLQ-R, indicating improved palatability. These findings demonstrate that CLQ-R preserves CLQ pharmacological activity while masking its bitter taste, supporting its potential as a pediatric-friendly antimalarial formulation.