Preparation and therapeutic application of docetaxel-loaded poly(d,l-lactide) nanofibers in preventing breast cancer recurrence.

ABSTRACT

The aim of this study was to develop docetaxel (DTX)-loaded poly-d,l-lactide (PDLLA) nanofibers and evaluate their therapeutic effect in preventing local breast cancer recurrence. DTX was incorporated into biodegradable PDLLA nanofibers by electrospinning. The surface morphology of the DTX/PDLLA nanofibers was characterized using scanning electron microscopy and wide angle X-ray diffraction. The in vitro release behavior of DTX from the fiber mats was also studied in detail. The cytotoxicity of DTX/PDLLA nanofibers was evaluated by MTT assay in 4T1 breast cancer cells. Flow cytometry revealed that DTX/PDLLA nanofibers exhibited apoptotic activity in 4T1 cells. In vivo antitumor efficacy of DTX/PDLLA nanofibers was evaluated in BALB/c mice bearing local breast tumors. Locoregional recurrence after primary tumor resection decreased obviously in mice treated with subcutaneously (16.7%) administered DTX-loaded PDLLA nanofibers, compared with the blank PDLLA nanofibers (88.9%), systemic (75.0%) or locally (77.8%) administered DTX and the control group (100%) (p < 0.05). Finally, after subcutaneous transplantation in mice, the DTX/PDLLA scaffolds presented excellent biocompatibility, as exhibited by the minimal presence of inflammatory cells in the region surrounding the scaffolds. Our results suggest that DTX/PDLLA nanofibers could have great potential for clinical application requiring local chemotherapy.