A Transferrin Receptor-Targeted Liposomal Formulation for Docetaxel

Transferrin receptor (TfR) is frequently over-expressed on epithelial cancer cells, TfR-targeted liposomes, therefore, can potentially improve tumor cell uptake, cytotoxicity, and treatment efficacy of the encapsulated drug. The liposomes loaded with docetaxel were prepared by polycarbonate membrane extrusion with the composition of hydrogenated soy phosphatidylcholine (HSPC)/egg phosphatidylcholine (PC)/cholesterol (Chol)/methoxy-polyethylene glycol (mPEG)(2,000)-distearoyl-phosphatidylethanolamine (DSPE) (HSPC/ePC/Chol/mPEG-DSPE) at the ratio of (10:75:10:5, mol/mol) and a drug-to-lipid ratio of 1:20, wt/wt. TfR-targeted liposomes were obtained by a post-insertion method with the ratio of Tf to phospholipid at 1:400 (mol/mol) and then lyophilized with sucrose as a lyoprotectant. TfR-liposomes exhibited enhanced stability for more than 6 months when stored as lyophilized cake. TfR-targeted liposomes of the same lipid composition entrapping calcein showed efficient uptake by K562 cells, which were TfR+. In vitro study of TfR-targeted liposomes containing docetaxel showed 3.6-fold greater cytotoxicity compared to non-targeted control liposomes in KB cells. Compared to docetaxel in Tween 80/ethanol formulation, the liposomal formulations showed much longer terminal half lives (6.37 h and 7.33 h for TfR-targeted and non-targeted, respectively). In conclusion, TfR-targeted liposomes might be a promising targeting delivery vehicle for TfR+ cancers and warrant further investigation.