Formulation and statistical optimization of Salvia hispanica L. Seed Polysaccharide/ chitosan nanoparticles for targeted delivery of quercetin in osteosarcoma

Achieving controlled drug release within the tumour microenvironment remains a major barrier to effective chemotherapy. The present study demonstrates the development of a low-cost, biodegradable nanocarrier that responds selectively to acidic tumour conditions, providing a safer alternative to current delivery systems. The hybrid nanoparticles were developed by the self-assembly of chitosan and Salvia hispanica L. seed polysaccharide, which combines the biocompatibility of natural polymers with intrinsic pH sensitivity. A bioactive flavonoid, quercetin, was successfully encapsulated within chitosan and Salvia hispanica L. seed polysaccharide nanoparticles with an efficiency of 78.8%. The fabricated nanoparticles had a size of 212 nm, an optimal size for passive tumour accumulation through the enhanced permeation and retention effect. A pH-responsive behaviour was observed, with significantly higher release calculated at pH 5.5 (acidic tumor microenvironment) compared to physiological pH 7.4. The kinetic modelling of release profile identified anomalous diffusion as the dominant mechanism under acidic conditions, while fickian diffusion was observed at physiological pH. The cell inhibition potential of quercetin loaded nanoparticles was assessed in U2OS osteosarcoma model. The cell viability assay confirmed that quercetin loaded nanoparticles retained potent metabolic inhibition, indicative of preserved bioactivity of quercetin post-encapsulation.