Journal article
Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release
Organic Chemistry, Department of Chemistry, Technical University of Denmark1
Department of Chemistry, Technical University of Denmark2
Colloids and Biological Interfaces Group, Self-organizing materials for nanotechnology Section, Department of Micro- and Nanotechnology, Technical University of Denmark3
Self-organizing materials for nanotechnology Section, Department of Micro- and Nanotechnology, Technical University of Denmark4
Department of Micro- and Nanotechnology, Technical University of Denmark5
The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm.
Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.
| Language: | English |
|---|---|
| Year: | 2010 |
| Pages: | 3782-3792 |
| ISSN: | 15204804 and 00222623 |
| Types: | Journal article |
| DOI: | 10.1021/jm100190c |
| ORCIDs: | Andresen, Thomas Lars , Madsen, Robert , Peters, Günther H.J. and Clausen, Mads Hartvig |
