Heparin-functionalized chitosan-poly(ε-caprolactone) nanoparticles loaded with quinine for selective targeting of infected erythrocytes and enhanced antiplasmodial efficacy.

AIMS: Malaria remains a major global health burden, particularly in sub-Saharan Africa. Although quinine (QN) is an effective antimalarial, its clinical application is limited by dose-dependent toxicity from nonspecific biodistribution. This study developed heparin-functionalized PCL nanoparticles (Hep-QN-PCL) to target Plasmodium falciparum-infected RBCs and enhance QN's therapeutic efficacy.

METHODS

QN-loaded PCL nanoparticles were formulated using a double emulsion solvent evaporation technique, followed by chitosan-mediated heparin conjugation. They were evaluated for physicochemical properties, in vitro drug release, hemolysis, cytotoxicity, targeting, and antiplasmodial activity against FCR3 Plasmodium falciparum.

RESULTS

Optimized Hep-QN-PCL nanoparticles (353.2 ± 16.8 nm, PDI 0.252, zeta +20.8 ± 1.9 mV, encapsulation 77.9%) showed successful Hep conjugation as confirmed through FTIR and thermal analysis, sustained QN release over 96 h via Fickian diffusion, and enhanced release under iRBC-mimicking conditions. They were hemocompatible (<4% hemolysis), less cytotoxic (LD50 >527 µg/mL vs. 195.7 µg/mL for free QN), and demonstrated increased iRBC targeting (partition 8.50 ± 0.30 vs. 4.20 ± 0.12). Hep-QN-PCL achieved ~5.3-fold higher antiplasmodial potency (IC50 = 23.33 ng/mL vs. 122.86 ng/mL) and 14.2-fold greater selectivity index (22.60 vs. 1.59).

CONCLUSION

These findings demonstrate a targeted nanomedicine platform with improved efficacy and safety for malaria therapy, suitable for further preclinical studies.