Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer

Abstract

Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+LL37 NPs using a water-in-oil-in-water double-emulsion solvent-evaporation method. Then, biodegradable and injectable thermosensitive PLA-L64-PLA hydrogel with lower sol-gel transition temperature at around body temperature was also prepared. Transmission electron microscopy revealed that the Doc+LL37 NPs formed with the PLA-L35-PLA copolymer were spherical. Fourier-transform infrared spectra certified that Doc and LL37 were encapsulated successfully. X-ray diffraction diagrams indicated that Doc was encapsulated amorphously. Intraperitoneal administration of Doc+LL37 NPs-hydrogel significantly suppressed the growth of HCT116 peritoneal carcinomatosis in vivo and prolonged the survival of tumor-bearing mice. Our results suggested that Doc+LL37 NPs-hydrogel may have potential clinical applications.