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.