Folate receptor-targeted drug delivery systems of doxorubicin for the treatment of cancer.

Supramolecular drug carriers are designed to accumulate in tumors by passive targeting via the enhanced permeability and retention (EPR) effect. The conjugation of targeting moieties results in receptor-mediated selective drug delivery. Folic acid (FA) is a low molecular weight ligand of the folate receptor (FR), widely used as targeting agent, due to overexpression of FR on many types of cancer cells1.In the present work, we compare the in vitro and in vivo pharmacological activity of two drug delivery systems bearing doxorubicin as the active drug and folic acid as the targeting moiety. In the first approach, two pullulan (Pull)-based prodrugs of doxorubicin (Dox) were synthesized, distinguished by the presence or absence of folic acid (FA) as targeting moiety, namely Pull-PEG-FA-Dox and Pull-PEG-Dox2. The second drug delivery system is the PEGylated liposomal doxorubicin (PLD, Doxil™) and its folate derivate obtained by ligand post-insertion from the commercial formulation (PLD-FA)3.