Folate targeting of drug carriers: a mathematical model.
The binding of folate-targeted drug carriers to a receptor-bearing cell surface is modeled using a deterministic approach. The model accounts for the presence of multiple folate ligands on the carrier surface, the anchoring and presentation of the ligands on flexible polymeric tethers, and the combination of both clustered and homogeneous spatial distributions of receptors on the cell surface. The model was validated against an experimental system where folate-bearing liposomes were used as delivery vehicles to deliver drug to tumor cells in vitro. Unknown parameters of the model were then estimated by a least-squares fit to the experimental data. A parametric study systematically varying the estimated parameters around the best-fit values indicated that the model was sensitive to these parameters, lending credence to their estimated values. This study indicates that drug uptake is dependent on several factors including the ligand number, the exposure time, and carrier concentration. For the specific case of folate targeting, the cumulative uptake of folate ligands is important, causing a decrease in the carrier uptake rate once a threshold cumulative uptake is crossed.
Ghaghada
Ketan B
KB
Department of Chemical Engineering, University of Houston, Houston, TX 77030, USA.
Saul
Justin
J
Natarajan
Jayaganesh V
JV
Bellamkonda
Ravi V
RV
Annapragada
Ananth V
AV
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008024:Ligands; D008081:Liposomes; D008954:Models, Biological; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008024:Ligands; D008081:Liposomes; D011956:Receptors, Cell Surface; D005492:Folic Acid