Co-delivery of hydrophilic gemcitabine and hydrophobic paclitaxel into novel polymeric micelles for cancer treatment

Abstract

This study was carried out to investigate an effective method for the co-delivery of Gemcitabine (GEM) and paclitaxel (PTX) into tumor cells. GEM and PTX were modified with functional (+)-α-tocopherol (VE) to obtain similar water solubility. Folic acid-poly(ethylene glycol)-(+)-α-tocopherol (FA-PEG-VE) was designed to co-encapsulate the modified GEM and PTX. Methoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (MPEG-PLGA) was used as a control. The characterizations of micelles were examined by DLS and TEM. It was found that two drugs-loaded FA-PEG-VE micelles, (GPF) and MPEG-PLGA micelles (GPM), had a spherical morphology with an average diameter of 127 nm and 118.9 nm, respectively. GEM-VE and PTX-VE encapsulation efficiencies of GPF were 91.09 ± 0.03%, 92.46 ± 0.02% (88.60 ± 0.03%, 89.32 ± 0.04% of GPM). In vitro release of GPF, 2.73% of GEM-VE and 2.88% of PTX-VE, were accumulatively released in 72 h (4.04% of GEM-VE and 3.88% of PTX-VE from GPM). Furthermore, comparisons of cytotoxicity were made with different fomulations. The IC50 of GPF after 72 h incubation was lowest. FA-PEG-VE micelle showed higher uptake efficiency than that of MPEG-PLGA micelle. Clathrin-mediated and energy-dependent endocytosis was involved in uptake mechanisms. These results demonstrated that GEM-VE and PTX-VE loaded FA-PEG-VE micelles would be a potentially useful prodrug-based nano-drug delivery system for cancer treatment.