ArticleACS omega2026
pH-Responsive Semi-IPN Nanoparticles Based on 4‑Carboxyphenylboronic Acid-Modified Chitosan for Targeted and Controlled Release of Chemotherapeutic Drug.
Article in ACS omega, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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