Enhanced Antimalarial Efficacy Obtained by Targeted Delivery of Artemisinin in Heparin-Coated Magnetic Hollow Mesoporous Nanoparticles

Abstract

Malaria is one of the deadliest infectious diseases threatening half of the world population. With the deterioration of the parasiticidal effect of the current antimalarials, novel approaches such as screening of more specific inhibitors and targeted delivery of drugs have been under intensive research. Herein, we prepare hollow mesoporous ferrite nanoparticles (HMFNs) of 200 nm with ferromagnetic properties using a one-pot hydrothermal reaction. A magnetically targeted drug-delivery system coloaded with artemisinin in the inner magnetite shell and heparin on the outer mesoporous shell (HMFN@ART@HEP) is developed. Specific targeting of the magnetic nanoparticles to the parasite-infected erythrocytes is achieved by the attraction between the HMFNs and hemozoin (paramagnetic), a vital metabolite of plasmodium in the erythrocytic stage. With the hemozoin production reaching the maximum during the schizont period of the parasite, HMFN@ART@HEPs are adsorbed to the infected red blood cells (iRBCs), which not only interferes with the release of merozoites but also significantly enhances the inhibitory efficacy due to the increased local concentration of artemisinin. Subsequently, the heparin coated on the surface of the nanoparticles can efficiently interfere with the invasion of freshly released merozoites to new RBCs through the specific interaction between the parasite-derived ligands and heparin, which further increases the inhibitory effect on malaria. As a cluster of heparin, heparin-coated nanoparticles provide stronger blocking capability than free heparin, resulting from multivalent interactions with surface receptors on merozoite. Thus, we have developed a HMFN-based delivery system with considerable antimalarial efficacy, which is a promising platform for treatment against malaria.

Potent Virustatic Polymer–Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo

“…Most efforts with respect to merozoite invasion inhibition have focused on soluble heparin-like polysaccharides. 16 − 19 Among the few nanoparticle studies, liposomes, 20 polymersomes, 21 and inorganic nanoparticles 22 have been trialed for inhibition of merozoite invasion in vitro . However, these antiparasitic nanoscale inhibitors were all heparin based and have struggled to meet the challenges of achieving high efficacy, in vivo applicability, and extended blood circulation half-lives.…”

Polymeric Nanoparticle Based Diagnosis and Nanomedicine for Treatment and Development of Vaccines for Cerebral Malaria: A Review on Recent Advancement

“…Artemisinin (ART) was loaded into the core–shell particle (HMFNs@ART@HEP), and specific targeting to infected RBCs was achieved due to the electrostatic attraction between HMFNs and hemozoin present in the metabolite of Plasmodium in the erythrocytic stage. These formulations not only interfere with the released merozoites but also help to increase the inhibitory efficacy …”

“…These formulations not only interfere with the released merozoites but also help to increase the inhibitory efficacy. 263 6.2. Nanopolymer Based Combination and Conjugation Therapies.…”

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…Other natural polymers that have attracted research interest for delivery purposes include, but are not limited to, glycogen [114][115][116], starch [114,[117][118][119][120], lignin [121,122], heparin [123,124], lentinan [14,125,126], and chondroitin sulfate [127][128][129].…”