Simultaneous delivery of docetaxel and tariquidar to chemoresistance cancer cells using functionalized lipid nanocarriers

Abstract Background The simultaneous administration of tariquidar (TRQ) with docetaxel (DTX) using a nanostructured lipid carrier (NLC) functionalized with PEG (5mol%) and RIPL peptide (PRN) was constructed to overcome the multidrug resistance caused by DTX administration alone. Results Either DTX or TRQ loaded PRN (D-PRN or T-PRN) and both DTX and TRQ loaded PRN (D/T-PRN) were prepared using the solvent emulsification evaporation technique. NLC samples showed homogeneous spherical morphology with nano-sized dispersion ( 95% EE and 73–78 µg/mg DL. In vitro cytotoxicity was concentration-dependent, and D/T-PRN exhibited the highest MDR reversal efficiency with the lowest combination index value. D/T-PRN increased the apoptotic cell death in MCF7/ADR cells by inducing cell cycle arrest in the G2/M phase. In a competitive cellular uptake assay, the single nanocarrier system exhibited better intracellular delivery efficiency of multiple probes to target cells compared to dual nanocarrier system. In the MCF7/ADR-xenografted mouse models, co-delivery with D/T-PRN significantly suppressed tumor growth compared to the other treatments. Conclusions Co-delivery of DTX/TRQ (1:1, w/w) using PRN will be a promising strategy against drug-resistant breast cancer cells.