Enhanced delivery of lenvatinib by hyaluronic acid-polyglycerol-stearate self-assembled micelles to inhibit hepatocellular carcinoma in vitro

CD44 protein is a well-known surface marker frequently observed in hepatocellular carcinoma (HCC) cells and plays crucial roles in the metastasis and invasion of the tumor. Hyaluronic acid (HA), an endogenous ligand, has the inherent ability to target and endocytosis into tumor cells via CD44 receptor-mediated internalization. The objective of this research was firstly to synthesize a hyaluronic acid-polyglycerol-stearate conjugate (HA-PG10C18), which was then used to self-assemble lenvatinib (Len)-loaded micelles (HA@Len-M) for improved delivery of Len to HCC. The micelles were developed applying a lyophilization-hydration approach. The physicochemical characteristics, including zeta potential, particle size distribution, encapsulation efficiency, morphology, stability and in vitro release were thoroughly assessed for the micelles. Additionally, in vitro cellular uptake studies demonstrated that HA@Len-M facilitated improved uptake of micelles in H22 tumor cells. Furthermore, an in vitro proliferation study of H22 cells showed that the cytotoxicity of HA@Len-M was stronger than other preparations, likely because of the highly efficient delivery to H22 cells by HA@Len-M. These findings suggest that HA@Len-M may offer a CD44 receptor-mediated drug delivery system for eradicating H22, thus representing a potential strategy for tumor-targeted chemotherapy procedures.