Folate targeting of drug carriers: a mathematical model.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Ghaghada, KB; Saul, J; Natarajan, JV; Bellamkonda, RV; Annapragada, AV
Published Date
- May 2005
Published In
Volume / Issue
- 104 / 1
Start / End Page
- 113 - 128
PubMed ID
- 15866339
Electronic International Standard Serial Number (EISSN)
- 1873-4995
International Standard Serial Number (ISSN)
- 0168-3659
Digital Object Identifier (DOI)
- 10.1016/j.jconrel.2005.01.012
Language
- eng