Heparin-Coated Dendronized Hyperbranched Polymers for Antimalarial Targeted Delivery

María San Anselmo, Elena Lantero, Yunuen Avalos-Padilla, Inés Bouzón-Arnáiz, Miriam Ramírez, Alejandro Postigo, José Luis Serrano, Teresa Sierra*, Silvia Hernández-Ainsa*, and Xavier Fernàndez-Busquets*. ACS Appl. Polym. Mater. 2023, 5, 1, 381–390

The rampant evolution of resistance in Plasmodium to all existing antimalarial drugs calls for the development of improved therapeutic compounds and of adequate targeted delivery strategies for them. Loading antimalarials in nanocarriers specifically targeted to the parasite will contribute to the administration of lower overall doses, with reduced side effects for the patient, and of higher local amounts to parasitized cells for an increased lethality toward the pathogen. Here, we report the development of dendronized hyperbranched polymers (DHPs), with capacity for antimalarial loading, that are coated with heparin for their specific targeting to red blood cells parasitized by Plasmodium falciparum. The resulting DHP–heparin complexes exhibit the intrinsic antimalarial activity of heparin, with an IC50 of ca. 400 nM, added to its specific targeting to P. falciparum-infected (vs noninfected) erythrocytes. DHP–heparin nanocarriers represent a potentially interesting contribution to the limited family of structures described so far for the loading and targeted delivery of current and future antimalarial compounds.