Biodendrimer Drug Delivery Vehicles
The container properties of dendrimers contribute to their use as vehicles for drug delivery. Recently, we have reported biocompatible polyester dendrimers composed of glycerol and succinic acid for the encapsulation of two anticancer agents: 10-hydroxycamptothecin (10HCPT) and 7-butyl-10-aminocamptothecin (BACPT). NMR experiments confirmed the encapsulation of the compounds within the dendrimer structure. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines (human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), non-small cell lung carcinoma (NCI H460), and glioblastoma (SF-268)) was determined, and low IC50s were measured for both camptothecins (see Figures). Cellular uptake and efflux measurements in MCF-7 cells also showed an increase of 16-fold and a 50% increase in drug retention within the cell when using the dendrimer vehicle.
Selected Publications
- “Therapeutic and Diagnostic Applications of Dendrimers for Cancer Treatment.”
Jesse B. Wolinsky and Mark W. Grinstaff
Advanced Drug Delivery Reviews, 2008, 60, 1037-1055 (invited review article). Link
- “Dendrimer-Encapsulated Camptothecins: Increased Solubility, Cellular Uptake, and Cellular Retention Affords Enhanced Anticancer Activity In vitro.”
Meredith T. Morgan, Yuka Nakanishi, David J. Kroll, Aaron P. Griset, Michael A. Carnahan, Michel Wathier, Nicholas H. Oberlies, G. Manikumar, Mansukh C. Wani, and Mark W. Grinstaff
Cancer Research, 2006, 66, 11913-11921. Link - “Dendritic Supramolecular Assemblies for Drug Delivery.”
Meredith T. Morgan, Michael A. Carnahan, Stella Finkelstein, Stephen J. Lee, and Mark W. Grinstaff
Chemical Communications, 2005, 4309-4311. Link - “Dendritic Molecular Capsules for Hydrophobic Compounds.”
Meredith T. Morgan, Michael A. Carnahan, Chad E. Immoos, Anthony R. Ribeiro, Stella Finkelstein, Stephen J. Lee, and Mark W. Grinstaff
Journal of the American Chemical Society, 2003, 125, 15485-15489. Link
Chemical structure of the [G4.5]-PGLSA-COONa dendrimer with encapsulated 10HCPT, (blue). Not drawn to scale.
Anticancer activity of dendrimer-encapsulated 10HCPT vs DMSO dissolved 10HCPT expressed as IC50s (nM). Data shown are the mean ± SD (n=3).
Anticancer activity of dendrimer encapsulated BACPT vs DMSO dissolved BACPT expressed as IC50s (nM). Data shown are the mean ± SD (n=3).