A novel self-assembled galactose/polysuccinimide-coated hydroxyapatite nanocarriers for targeted hepatic doxorubicin delivery

To mitigate the adverse effects of doxorubicin (DOX) during the treatment of liver cancer, this study aimed to develop a novel DOX-encapsulated active-targeted nanodelivery system. The auxiliary materials hydroxyapatite (HAP), polysuccinimide (PSI), galactose-modified polyethylene glycol (Gal-PEG), PSI covalently linked with three different mole ratios of polyethylene glycol (PEG-PSIs), and galactose covalently linked with PEG-PSIs (Gal-PSIs) were synthesized and structurally characterized. The Box-Behnken and Three-Level Factorial Design response surface methodologies were employed to optimize the formulations and synthesis protocols for DOX@HAP/PSI (DOX@DC, where DC denotes the drug carrier), DOX@PEG-DCs, and DOX@Gal-DCs. The in vitro drug release and in vivo tissue distribution of each formulation were examined. Furthermore, in vitro studies were conducted to examine the effects of these formulations on the proliferation, apoptosis, and migration of Huh-7 liver cancer cells. The formulations and synthesis protocols for different DOX-based preparations were optimized. All nanoparticles gradually released DOX at pH levels >5, with the release rate increasing with the pH value. Among the tested formulations, DOX@Gal-DC20 (mole ratio of Gal-PEG to PSI = 1:20) showed the best hepatic targeting in mice in vivo. Furthermore, in vitro pharmacodynamic experiments indicated that Gal-DC20 had low cytotoxicity, could be taken up by cancer cells, and could significantly inhibit the proliferation of Huh-7 cells. Hemolysis experiments confirmed that none of the prepared formulations induced hemolysis. The novel nanodelivery system established in the study (DOX@Gal-DC) is simple to prepare and shows significant hepatic targeting.