Preferential targeting of human erythrocytes infected with the malaria parasite Plasmodium falciparum via hexose transporter surface proteins

  • Heikham K
  • Gupta A
  • Kumar A
 et al. 
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Abstract

Glucose uptake by Plasmodium-infected erythrocytes (RBC) is higher compared to uninfected RBC. Glucose is transported across the cell membrane by transporter proteins. Particles of median size 146.3 ± 18.7 nm, containing anti-malarial agents in corn starch were prepared for investigating: (a) whether the glucose moiety in starch targets RBC via hexose transporter(s), (b) whether there are differences in the extent of targeting to uninfected RBC versus infected RBC (iRBC) in view of higher cell surface density of these proteins on iRBC and (c) whether targeting provides enhanced efficacy against P. falciparum in comparison to drugs in solution. Binding of these particles to RBC was target-specific, since it could be blocked by phloretin, an inhibitor of glucose transporters (GLUT), or competed out in a dose-dependent manner with d-glucose in a flow cytometry assay. Significant (P = 0.048, t-test) differences in extent of targeting to iRBC versus RBC were observed in flow cytometry. CDRI 97/63 incorporated in particles was 63% more efficacious than its solution at 250 ng/ml, while quinine was 20% more efficacious at 6.25 ng/ml in a SYBR Green incorporation assay. Preferential targeting of iRBC using an inexpensive excipient promises advantages in terms of dose reduction and toxicity alleviation.

Author-supplied keywords

  • Flow cytometry quinine
  • GLUT1
  • Malaria
  • Nanoparticles
  • PfHT-1
  • Starch
  • Trioxane

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Authors

  • Kajal Devi Heikham

  • Ankit Gupta

  • Ambrish Kumar

  • Chandan Singh

  • Juhi Saxena

  • Kumkum Srivastava

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