MPEG-PDLLA polymeric micelles loading a novel pyridazinone derivative IMB5036 for improving anti-tumor activity in hepatocellular carcinoma

Abstract

IMB5036 (N7) is a hydrophobic pyridazinone compound with antitumor activity, identified in our laboratory. To increase its water solubility, we utilized nanomicelles encapsulating N7 in this study. Monomethyl polyethylene glycol-polylactic acid (mPEG-PDLLA) polymer micelles were employed as drug carrier, and their characterizations were measured. IMB5036/mPEG-PDLLA (N7M) exhibited a particle size of approximately 28 nm and a polydispersity index of around 0.2. The optimal dosage ratio of N7 to mPEG-PDLLA was determined to be 10:90, with an encapsulation rate of (93.66 ± 3.94)% and a drug loading efficiency of (9.59 ± 1.26)%. The morphology of N7 micelles was spherical, with a uniform particle size distribution and good water solubility of approximately 1.17 mg/ml. Compared to the free drug, N7M demonstrated a higher tumor cell uptake rate and slow release profile, while maintaining similar tumor cell killing ability and apoptosis-inducing capacity. In vivo experiments confirmed that the nanomicelles improved tumor targeting, and N7M effectively inhibited tumor growth in a hepatoma xenograft model. Overall, N7M represents a successful injectable nanomicelle formulation for the treatment of hepatoma.