Self-assembled polymeric prodrug provides controlled cisplatin release and enhanced efficiency in local chemotherapy.

In this work, we report the synthesis of novel polymeric prodrug nanoparticles of cisplatin to reduce the severe side effects of cisplatin and investigate its potential localized delivery to aerodigestive tract carcinomas. Cisplatin was conjugated to succinylated poly(vinyl alcohol) (PVA-SA) via coordinate ester linkages. The abundance of residual hydroxyl (-OH) and carboxyl (-COOH) groups along the polymer backbone facilitated spontaneous nanoparticle self-assembly through ester bond crosslinking in a straightforward, one-pot reaction. Successful polymer modification and drug conjugation were confirmed using FTIR and EDX measurements. The in vitro cisplatin drug release studies were carried out over two weeks under physiological conditions (PBS, pH 7.4). The results showed that free cisplatin exhibited rapid release (k´=0.00829 h‒1), whereas the polymeric cisplatin prodrug demonstrated a significantly sustained release profile (k´=0.00046 h‒1), indicating its potential to reduce cisplatin-release side effects. Kinetic modelling of the release data revealed that the Korsmeyer-Peppas kinetic model provided the best fit, suggesting a combined diffusion- and erosion-controlled release mechanism. The anticancer activity of the polymeric cisplatin prodrug was evaluated using an MTT assay against two cancer cell lines (A549 and Hep-2). The polymeric cisplatin prodrug exhibited lower IC50 values (0.00122±0.00069 and 0.00079±0.00031 μM) compared to free cisplatin (0.00434±0.00134 and 0.00218±0.00074 μM) for A549 and Hep-2 lines, respectively. While limited to in vitro models and indirect mucoadhesion evidence, these findings suggest that the developed biocompatible system is a promising delivery platform for further evaluation in localized chemotherapy.