Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7α-APTADD to breast cancer cells

Transferrin (TO-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7 alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17-dione (7 alpha-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3 +/- 3.4%, mean diameter of 170.3 +/- 7.6 nm and zeta potential of 18.9 +/- 1.5 mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC50 value of the Tf-nanoparticles was ranging from 0.77 to 1.21 nM, and IC50 value of the nanoparticles was ranging from 1.90 to 3.41 nM (n = 3). The former is significantly lower than the latter (p < 0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors. (C) 2010 Elsevier B.V. All rights reserved.