PEGylated hyaluronic acid-coated liposome for enhanced in vivo efficacy of sorafenib via active tumor cell targeting and prolonged systemic exposure.

ABSTRACT

This study aimed to design an effective formulation for enhancing the tumor-targeted delivery of sorafenib. Three sorafenib-loaded liposomal formulations including uncoated liposome (SF-Lip), hyaluronic acid-coated liposome (HA-SF-Lip), and PEGylated hyaluronic acid-coated liposome (PEG-HA-SF-Lip) were developed with narrow size distribution and high encapsulation efficiency. The cellular uptake and cytotoxicity of HA-SF-Lip and PEG-HA-SF-Lip were greater than those of SF-Lip in MDA-MB-231 cells overexpressing CD44, whereas there were no significant differences in MCF-7 cells with low CD44 expression, indicating the CD44-mediated cellular uptake of coated liposomes. In comparison with sorafenib solution, PEG-HA-SF-Lip increased the systemic exposure and plasma half-life in rats by 3-fold and 2-fold, respectively. Consistently, PEG-HA-SF-Lip was the most effective for tumor growth inhibition through CD44 targeting in the MDA-MB-231 tumor xenograft mouse model. Taken together, the present study suggests that PEG-HA-SF-Lip might be effective for the tumor-targeted delivery of sorafenib with enhanced systemic exposure and longer blood circulation.