Folate Conjugated Micellar Carriers for Targeted Drug Delivery

Document Type




Conference Title

American Association for Pharmacutics (AAPS)


American Association for Pharmacutics (AAPS)


Nashville, TN

Conference Dates

November 6-10, 2005

Date of Presentation



Purpose. To the test the hypothesis that folate conjugated amphiphilic micelles can effectively target drugs to folate receptor overexpressing cells.

Methods. Folate labeled amphiphile (F-Peg-C) was prepared by conjugating decanoic acid to one end of triethylene glycol diamine by amide linkage followed by coupling the monoamine to the free carboxylic groups in folic acid by carbonyldimidazole in anhydrous DMF. The amphiphile is purified by thoroughly washing with alcohol to remove imidazole and unreacted amine followed by washing with an alkaline buffer (50mM K2HPO4, pH 8.4) to remove unreacted folic acid. The purity of the product is checked by HPLC and the formation of the compounds was verified by MALDI-TOF mass spectrometry. Critical micellar concentration (CMC) for the amphiphiles was determined by the pyrene fluorescence method in 50mM K2HPO4 buffer. A lipophilic model drug, Paclitaxel, was encapsulated in the micelles and the efficacy of the delivery system was tested by cytotoxicity assay (SRB assay) against folate receptor over-expressing HeLa cells. CaCO2 cells with lowerexpressed folate receptors were used as control in the cytotoxicity evaluation.

Results. The yield of folate conjugated amphiphiles was 82% based on folic acid used. IC50 of paclitaxel delivered by folate conjugated micelles was significantly lower (0.023 microM) than the control (IC50=0.055 microM for the same amount of paclitaxel in aqueous solution) in cytotoxicity studies using HeLa cells. Whereas treatment of CaCO2 cells with free drug and folate conjugated micelle encapsulated drug showed no statistical differences in cytotoxicity profiles.

Conclusion. In HeLa cells, a lower dose of paclitaxel from folate labelled amphiphiles achieved the same level of cytotoxicity when compared to its aqueous solution. Therefore, the folate conjugated amphiphile has potential to effectively target drugs to folate receptors overexpressing cancer cells.

This document is currently not available here.