Preparation and optimization of biotin-conjugated chitosan-coated rosin nanoparticles for targeted delivery of dasatinib in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a fatal form of liver cancer. Dasatinib (DST), a tyrosine kinase inhibitor, has shown anti-proliferative and apoptotic effects against HCC cells. However, its clinical application is limited by its poor water solubility and adverse effects. This study aimed to encapsulate DST in targeted nanoparticles using biocompatible and cost-effective materials to improve its solubility, cellular uptake, and cytotoxicity. DST-loaded rosin nanoparticles (DST/ROS) were prepared by nanoprecipitation and optimized using the Box-Behnken design. For active targeting, chitosan (CTS) was conjugated with biotin (BTN), and the optimized DST/ROS nanoparticles having a particle size of 269.2 ± 9.6 nm, zeta potential of -1.69 ± 0.04 mV and entrapment efficiency of 96.9 ± 2.8 were coated with the CTS-BTN. DST/ROS/CTS-BTN nanoparticles had a positive zeta potential (+ 13.3 ± 1.7 mV) and particle size of 284.0 ± 11.4 nm. The CTS-BTN coating improved colloidal stability and provided a more controlled drug release profile with lower burst release. BTN-targeted drug-loaded nanoparticles demonstrated significantly higher cellular uptake and improved cytotoxicity against HepG2 cells compared to non-targeted drug-loaded nanoparticles and free DST, as confirmed by flow cytometry and MTT assays. Consequently, the designed drug delivery system was successful in improvement of in vitro DST therapeutic effects on HCC cell line, HepG2. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026.