Folate appended cyclodextrins for drug, DNA, and siRNA delivery

Drug, DNA, and siRNA delivery systems based on cyclodextrin (CD) core and connected with folate (FA) via various linkers are presented. They include simple mono-derivatized cyclodextrins as well as cyclodextrins with higher degree of substitution, both in their primary and secondary sides. Examples of simple polymers and dendrimers are also discussed. Such carriers possess properties inherent to both of their components. Cyclodextrin provides the ability to encapsulate organic molecules in its inner cavity, thus improving their solubility in water, bioavailability, and stability, while FA assures targeting folate receptor overexpressing cancer cells. Drug delivery systems loaded with drugs such as e.g. methotrexate, doxorubicin, paclitaxel, vinblastine, and docetaxel were found to have superior properties as compared to the free drug. Dendritic folate appended cyclodextrins were also found to be good sustained release systems for DNA and siRNA. The recent progress in the synthesis and drug, DNA, and siRNA delivery application of folate appended cyclodextrins is presented.