Targeted therapy of gastric cancer with gingerol-loaded hyaluronic acid/PEG-coated PLGA nanoparticles: Development and physicochemical evaluation

Abstract

In recent years, nanoparticle (NP)-based drug delivery systems have emerged as promising candidates for targeted therapy due to their ability to enhance drug bioavailability and delivery of therapeutic agents to tumor sites. Herein, we aim to develop gingerol-hyaluronic acid (HA)-poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-NPs (gingerol-HA-NPs) as a targeted therapy for gastric cancer. To target the CD44 receptor expressed on malignant cells, gingerol-HA-NPs were fabricated using a single-emulsion solvent evaporation method. The physicochemical properties and cytotoxicity of the NPs were characterized, and their cellular uptake was assessed using flow cytometry analysis. Flow cytometry analysis of FITC-labeled annexin V/PI-stained cells was used to evaluate the induction of apoptosis/necrosis by the NPs. In vitro release studies demonstrated sustained and controlled release of gingerol from the NPs over 72 h. The release kinetics followed the Peppas-Korsmeyer model, suggesting that drug release was influenced by polymer erosion and disentanglement. Also, the NPs showed dose-dependent cytotoxic effects on MKN cells, with lower IC50 values than plain gingerol. The IC50 values for gingerol-PLGA-PEG-NPs (gingerol-NPs) and gingerol-HA-NPs were 175 μM and 117 μM, respectively after 48 h, while the IC50 value for plain gingerol was 202 μM. Gingerol-HA-NPs exhibited higher cellular uptake in MKN cells (CD44+) compared to plain drug and gingerol-NPs. The uptake increased with prolonged incubation. The analysis of apoptosis/necrosis detection showed that the gingerol-HA-NPs caused a greater occurrence of late apoptosis (An+/PI+) in MKN cells compared to plain gingerol and gingerol-NPs, with percentages of 76.43 %, 11.58 %, and 24.03 % respectively. These results underscore the potential of gingerol-HA-NPs as a promising targeted therapy for the treatment of gastric cancer.