Injectable corilagin/low molecular weight chitosan/PLGA-PEG-PLGA thermosensitive hydrogels for localized cancer therapy and promoting drug infiltration by modulation of tumor microenvironment.

Abstract

The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA-PEG-PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment. The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.