Aditi A Sidhaye1, Kanchan C Bhuran1, Sneha Zambare1, Munna Abubaker2, Niroshini Nirmalan2, Kamalinder K Singh1,3. 1. CU Shah College of Pharmacy, SNDT Women's University, Santacruz (W), Mumbai 400049, India. 2. School of Environment & Life Sciences, University of Salford, Manchester, M5 4WT, UK. 3. School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
Abstract
AIM: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. METHODS: Artemether-loaded nanoparticles (AANs) were designed and antimalarial activity evaluated in vitro/in vivo using Plasmodium falciparum/Plasmodium berghei species, respectively. RESULTS: Selective internalization of AAN into Plasmodium-infected RBCs in preference to healthy erythrocytes was observed using confocal imaging. In vitro studies showed 50% dose reduction for AAN as compared with drug-only controls to achieve IC50 levels of inhibition. The nanoparticles exhibited twofold higher peak drug concentrations in RBCs with antimalarial activity at 50% of therapeutic doses in P. bergei infected mice. CONCLUSION: Novel HSA-based nanoparticles offer safe and effective approach for selective targeting of antimalarial drugs.
AIM: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. METHODS:Artemether-loaded nanoparticles (AANs) were designed and antimalarial activity evaluated in vitro/in vivo using Plasmodium falciparum/Plasmodium berghei species, respectively. RESULTS: Selective internalization of AAN into Plasmodium-infected RBCs in preference to healthy erythrocytes was observed using confocal imaging. In vitro studies showed 50% dose reduction for AAN as compared with drug-only controls to achieve IC50 levels of inhibition. The nanoparticles exhibited twofold higher peak drug concentrations in RBCs with antimalarial activity at 50% of therapeutic doses in P. bergei infected mice. CONCLUSION: Novel HSA-based nanoparticles offer safe and effective approach for selective targeting of antimalarial drugs.
Entities:
Keywords:
artemether; human serum albumin nanoparticles; malaria; parasitized RBCs