Injectable and In Situ-Formable Thiolated Chitosan-Coated Liposomal Hydrogels as Curcumin Carriers for Prevention of In Vivo Breast Cancer Recurrence.

Abstract

To improve water solubility and bioavailability, curcumin (Cur) was encapsulated by liposomes (Cur-Lip), which was further coated with thiolated chitosan (CSSH) to form liposomal hydrogels (CSSH/Cur-Lip gel). The hydrogels were thermosensitive with in situ injectable performance, which were fluidic at room temperature and gelled quickly at 37 °C. The cumulative release ratio of the 200 μM CSSH/Cur-Lip gel was 31.57 ± 1.34% at 12 h, which could effectively delay the release of curcumin. Worthily, the resilient hydrogels were compressive even after five cycles of compression. The cytotoxicity test indicated that the liposomal hydrogels had good cytocompatibility, but after encapsulation of curcumin, MCF-7 cells were suppressed and killed dramatically after 72 h. The in vivo breast cancer recurrence experiment showed that the CSSH/Cur-Lip gel inhibited breast cancer recurrence after tumors were resected, and the tissue of defect in the CSSH/Cur-Lip gel group was repaired. The results showed that the drug-loaded liposomal hydrogels can deliver curcumin continuously and exerted an excellent tumoricidal effect in vitro and in vivo. The injectable, in situ-formable, and thermosensitive CSSH/Cur-Lip gel can be designed as a promising novel drug delivery vehicle to be used as carriers for local accurate and sustained drug delivery to minimize burst release and as tissue engineering scaffolds for tissue regeneration after tumor resection.