AI-guided data-driven kinetic modelling carbon quantum dot-enabled pH-responsive CMC/CeO ₂ nanocarriers for quercetin delivery and in vitro evaluation in lung cancer cells

This work reports the development and systematic evaluation of a carboxymethyl cellulose (CMC)-based nanocarrier system co-loaded with cerium oxide (CeO2) and carbon quantum dots (CQDs) for pH-responsive delivery of quercetin (QC) and in vitro evaluation in lung cancer cells. The nanocarriers were prepared using a water-in-oil-in-water (W/O/W) double emulsion approach, yielding spherical particles with an average size of approximately 134 nm and a high positive surface charge (+66 mV), indicative of favourable colloidal stability. FESEM analysis confirmed a uniform morphology and compact internal structure. The incorporation of CeO2 appears to reinforce the polymer matrix, contributing to improved drug encapsulation. The optimized formulation exhibited high encapsulation efficiency (88%) and drug loading capacity (47%), outperforming CeO2-free systems. In vitro release studies demonstrated a clear pH-dependent biphasic behaviour, with significantly faster release under pH 5.4 compared to physiological pH (7.4), reaching 98% and 58% after 96 h, respectively. Drug release followed the Higuchi model, suggesting diffusion-controlled kinetics, while the Korsmeyer–Peppas model indicated a non-Fickian mechanism. An AI-guided nonlinear modelling workflow was used to extract interpretable kinetic descriptors directly from experimental release data. Biological evaluation revealed enhanced anticancer activity against A549 cells, with viability reduced to 49.1%, while maintaining high biocompatibility towards L929 cells.