Hyaluronic-Acid-Coated Sterosome for Dasatinib Delivery in Hepatocellular Carcinoma: Preparation, Physicochemical Characterization, and In Vitro Evaluation.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and treatment remains challenging due to high recurrence rates, resistance to chemotherapy, and severe side effects. Dasatinib (Das) has shown therapeutic potential against HCC, but its clinical use is limited by poor bioavailability and short half-life (~3-4 h). Here, we developed a hyaluronic acid (HA)-coated sterosome for targeted and sustained delivery of Das to CD44-overexpressing HCC cells. Sterosomes composed of octadecylamine and cholesterol at a 5:5 (v/v) ratio were prepared via thin-film hydration and sonication, yielding stable particles (~90 nm) with high encapsulation efficiency (EE ~72%) for uncoated vesicles and ~58% after HA coating. HA-sterosomes (HA-St-Das) exhibited a uniform size (≈200 nm) and negative surface charge (-26 mV), with improved storage stability and resistance to lyophilization. In vitro release studies demonstrated pH-responsive Das release accelerated under acidic conditions (pH 6.0-5.0), mimicking tumor and lysosomal environments. In HepG2 cells, HA-St-Das exhibited enhanced cytotoxicity (IC50 ~7.0 μM) and prolonged intracellular retention compared to free Das and uncoated carriers. Fluorescence microscopy confirmed receptor-mediated uptake via CD44, leading to gradual and sustained intracellular delivery. Overall, the HA-St-Das system provides biocompatible, targeted, and controlled Das delivery, addressing key limitations of current liver cancer therapies and representing a promising nanomedicine platform for further development.