The blood stage of malaria, where Plasmodium parasites invade red blood cells, accounts for most clinical symptoms and severe complications. However, current drugs and vaccines remain limited by drug resistance, toxicity, poor stability, and reduced overall efficacy. This review aimed to synthesize evidence on nanotechnology-based delivery systems for improving targeting specificity, enhancing drug and antigen stability, and optimizing therapeutic outcomes. Forty (40) studies from 2005 to 2025 were systematically analyzed, focusing on lipid, polymeric, inorganic, and protein-based nanoparticles targeting the blood stage. Results showed that functionalized nanocarriers with ligands targeting infected red blood cells significantly enhanced drug efficacy and reduced systemic toxicity. In vaccine development, nanoparticles used as antigen carriers elicited strong immune responses, achieving up to 83.3 % survival in in vivo preclinical models. Despite these promising outcomes, challenges such as scalable production, clinical translation, and regulatory approval persist. Overall, the findings highlight nanomedicine's transformative potential for malaria treatment and prevention.
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