Design and preparation of PLA-chitosan-PEG-glucose copolymer for combined delivery of Paclitaxel and siRNA

Abstract In recent years, the use of cell surface receptors for targeted nanoparticle delivery to cancer cells has emerged as a new strategy that enhances drug effectiveness by minimizing nonspecific absorption in healthy cells and reducing side effects. This study focused on dual-purpose chitosan-polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles, which target glucose to improve the delivery of Paclitaxel (PTX) and small interfering RNA-fluorescein amidite (siRNA-FAM) to cancer cells. The PLA-chitosan-PEG-glucose (Glu) copolymer was synthesized by binding chitosan-PLA and PEG-Glu, and then was characterized via Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy, confirming successful synthesis. The FTIR results indicated successful copolymer formation. The solvent diffusion technique involves the encapsulation of PTX and siRNA-FAM within the nanoparticles. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were employed to analyze the morphology, size, and surface charge of the nanoparticles. SEM images revealed that the nanoparticles had a spherical structure, and DLS analysis indicated an average size of approximately 188 nm. The biocompatibility of the nanoparticles was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and their drug transport ability was evaluated via flow cytometry. The results demonstrated that the PLA-chitosan-PEG-Glu copolymer exhibited low toxicity due to the combination of PLA and PEG, while the efficiency of siRNA-FAM transport was significantly greater than that of uncoated RNA. Graphical abstract