Folate-decorated poly(lactide-co-glycolide)-vitamin E TPGS nanoparticles for targeted drug delivery.

Doxorubicin-loaded nanoparticles (NPs) of vitamin E TPGS-folate (TPGS-FOL) conjugate and doxorubicin-poly(lactide-co-glycolide)-vitamin E TPGS (DOX-PLGA-TPGS) conjugate were prepared by the solvent extraction/evaporation method for targeted chemotherapy of folate-receptor rich tumors. X-ray photoelectron spectroscopy demonstrated that folate was distributed on the NP surface while the drug molecules were entrapped in the NP matrix. The NPs were found of approximately 350nm diameter and exhibited a biphasic pattern of in vitro drug release. The cell uptake of the fluorescent NPs and the cell viability of the drug formulated in the NPs were quantitatively investigated, which were found dependent on the content of targeting TPGS-FOL conjugate. The NPs of 50% TPGS-FOL showed cellular uptake by MCF-7 cells 1.5 times higher and by C6 cells 1.7 times higher than the NPs with no TPGS-FOL component after 30min incubation. The MCF-7 cell viability was found decreased significantly from 50.8% for the drug-loaded NPs of no TPGS-FOL to 8.2% for those of 50% TPGS-FOL after incubation at 100microug concentration at 37 degrees C. The latter NPs also exhibited much lower IC(50) value than the DOX after 24h incubation, i.e., 19.4 vs. 43.7micror MCF-7 cells and 3.3 vs. >100micror C6 cells.