Development and evaluation of redox-responsive alginate-SS-ibuprofen derivative based anti-tumor target drug delivery system for the controlled release of doxorubicin

Nowadays, self-assembled polymeric micelles from amphiphilic polymer conjugates are urgently needed to enhance drug targeting and release efficiency. On account of the excellent properties of alginate and the redox-responsiveness of disulfide bonds, a redox-sensitive alginate-SS-ibuprofen derivative (LSA-SS-IBU) based anti-tumor target drug delivery system was created by attaching the hydrophobic ibuprofen (IBU) onto the hydro-philic alginate molecular skeleton through disulfide linkages for glutathione (GSH) triggered delivery of doxo-rubicin hydrochloride (DOX). The structure and self-assembly behavior of the synthesized LSA-SS-IBU was systematically evaluated by FT-IR spectrometer, 1H NMR spectrometer, fluorescence spectrophotometer (FM), transmission electron microscope (TEM) and dynamic light scattering (DLS). Furthermore, the in vitro release of drugs from the LSA-SS-IBU micelles loaded with DOX was examined, along with the assessment of their cyto-toxicity to HeLa cells. The resultant LSA-SS-IBU had a critical micelle concentration (CMC) value of 0.19 mg/mL that was able to self-assemble into the spherical micelles with the particle size and zeta potential of 148.2 +/- 4.3 nm (PDI = 0.25) and-47.2 +/- 0.4 mV, respectively. At a mass ratio of 3:10 for DOX/LSA-SS-IBU, the LSA-SS-IBU micelles achieved drug loading ratio (DLR) and encapsulation efficiency (EE) values of 12.2 % and 46.3 %, respectively. Furthermore, the in vitro drug release study indicated that the total drug release percentage of the drug-encapsulated LSA-SS-IBU micelles in PBS with the presence of 10 mmol/L GSH for 12 h exceeded 67.0 %, demonstrating a substantial increase compared to that in GSH-free PBS. The in vitro cytotoxicity findings indicated that LSA-SS-IBU had good biocompatibility, while the IC50 value and the cell viability of DOX-loaded LSA-SS-IBU micelles cultured with HeLa cells for 48 h was 2.2 mu g/mL and less than 20.1 %, respectively, which could significantly inhibit the growth of HeLa cells. Therefore, redox-responsive LSA-SS-IBU micelles had po-tential applications in cancer therapy for hydrophobic anti-tumor drug delivery.