Co-encapsulation of antimalarial drug and SPIO in glucose-conjugated polymeric micelles against parasite-infected erythrocytes

Abstract

Malaria, a life-threatening infectious disease transmitted through bites of Anopheles mosquitoes, remains a major global health challenge. The erythrocytic stage of malaria, where the parasite undergoes multiplication within red blood cells, is crucial for disease progression. Targeting this stage is essential for effective treatment and eradication of the parasite. However, the emergence of drug resistance highlights the need for innovative therapeutic approaches. Furthermore, accurate detection and tracking of parasites are imperative for confirming complete parasite eradication. Enhancing drug efficacy and specifically targeting molecular entities are key strategies to address this challenge. To combat the disease, a drug delivery system was developed to encapsulate the drug along with contrast agents. This system was conjugated with glucose to target both new permeable pathways (NPPs) and the Plasmodium falciparum hexose transporter (PfHT). In this study, glucose-conjugated polymeric micelles containing superparamagnetic ironoxide (SPIO) nanoparticles and quinine were synthesized and characterized. These micelles demonstrated hemocompatibility and exhibited superior drug release profiles under acidic conditions mimicking the parasite's environment. In vitro studies on infected red blood cells (RBCs) revealed targeted micelles enhanced antimalarial activity compared to non-targeted micelles and free drug. Additionally, targeted micelles exhibited the highest fluorescence signal intensity and MRI contrast enhancement. Based on these results, glucose/quinine/SPIO micelles hold significant promise for tracking and treatment functions in malaria, offering precise detection and targeted drug delivery to eradicate the parasite effectively.