Chitosan nanoparticle-based drug delivery systems incorporating 4-carboxy-phenylboronic acid (PBA) have emerged as a key strategy for enhancing therapeutic efficacy by active targeting of tumor and improving drug loading capacity. Herein, we have developed a PBA-modified chitosan-based (PBA-CS) semi-interpenetrating polymer network (semi-IPN) nanoparticles (NPs) of 4-carboxy-phenylboronic acid-conjugated chitosan-poly-(1-vinylimidazole) (PBA-CS-PVIm) and 4-carboxy-phenylboronic acid-conjugated chitosan-poly-(methacrylic acid) (PBA-CS-PMAA) via free radical polymerization of 1-vinyl imidazole (VIm) and methacrylic acid (MAA), with high drug loading capacity of doxorubicin (Dox). The synthesized semi-IPN NPs were characterized using Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). TEM analysis revealed that the Dox-loaded semi-IPN NPs were spherical with an average diameter of 33.86 nm for PBA-CS-PVIm and 31.28 nm for PBA-CS-PMAA. Correspondingly, DLS measurements showed high positive surface charges, with zeta potentials of +41.1 and +35.9 mV, respectively. The PBA-CS-PVIm semi-IPN NPs showed a higher loading capacity (LC) and encapsulation efficiency (EE) of 180 ± 6 mg/g and 66 ± 3%, respectively, for Dox at pH 5.5, while the LC and EE of PBA-CS-PMAA semi-IPN NPs are 100 ± 5 mg/g and 60 ± 4%, respectively. The pH-responsive biological macromolecules (PBA-CS, PMAA, and PVIm) effectively enabled sustained drug release, resulting in 78% of Dox being released from PBA-CS-PMAA and 65% from PBA-CS-PVIm over 120 h. The faster release from PBA-CS-PMAA was attributed to electrostatic repulsion between Dox and NPs, while the slower release from PBA-CS-PVIm was due to π-π stacking interactions. The semi-IPN NPs demonstrated excellent biocompatibility in Vero cells, whereas Dox-loaded NPs produced significant cytotoxicity in HeLa cells (80%-95%) when incubated for 48 h. Kinetics studies revealed that the release of Dox follows diffusion and polymer relaxation mechanisms, fitting both the Higuchi and Korsmeyer-Peppas models. These results demonstrate the potential of PBA-CS-based semi-IPN NPs as efficient nanocarriers for chemotherapy.
Hasnat et al. (2026) studied this question.