Honokiol nanosuspensions loaded thermosensitive hydrogels as the local delivery system in combination with systemic paclitaxel for synergistic therapy of breast cancer.

Local administration of therapeutic agents provides a favorable approach to enhance drug accumulation at pathological sites. In this study, a novel honokiol nanosuspensions loaded thermosensitive injectable hydrogels (HK-NS-Gel) was designed as the local delivery system for the combination therapy with systemic paclitaxel (PTX). The formed HK-NS-Gel showed superior gelation time and temperature. In vitro release and in vivo drug retention assay showed that HK-NS-Gel can slowly and steadily release the HK during 12 days. Meanwhile, enhanced PTX accumulation in the tumor was observed after intratumoral injection of HK-NS-Gel. In vitro cytotoxicity and cell apoptosis tests against 4T1 cells proved the synergistic effects of free PTX combined with HK-NS-Gel. In vivo antitumor study was conducted on 4T1 bearing mice, indicating that co-administration HK-NS-Gel and PTX could effectively enhance tumor growth suppression, and the tumor inhibitory rate was as high as 72.51%. In conclusion, intravenous delivery of PTX combined with intratumoral delivery of HK-NS-Gel was a promising combination for breast cancer therapy with enhanced therapeutic response and safety.