Surface-Engineered PLA-Based Nanoparticles via Folic Acid–Functionalized Chitosan Coatings: Performance Evaluation and Targeted Drug Delivery Potential

Surface engineering of biodegradable polymeric nanoparticles offers an effective strategy to regulate interfacial properties, biological interactions, and functional performance in advanced coating systems. In this work, poly(D,L-lactic acid) (PLA)-based nanoparticles were surface-engineered using a folic acid–functionalized chitosan (CS-FA) coating, creating a hybrid organic architecture that integrates biodegradability, biofunctionality, and receptor-specific surface recognition.

The impact of the CS-FA coating on surface and coating performance metrics was systematically investigated. Structural and chemical modification were confirmed by FTIR and NMR spectroscopy, while particle morphology and coating integrity were evaluated by SEM and DLS. Key interfacial properties, including wettability and enzymatic degradation, were assessed under physiological conditions (pH 7.4), demonstrating that FA-functionalized chitosan coatings impart enhanced surface hydrophilicity, a feature that can directly influence diffusion characteristics and stability of the coated nanoparticles. Furthermore, to evaluate biointerface performance, in vitro studies were conducted using immortalized mouse embryonic fibroblasts (iMEFs) and MDA-MB-231 breast cancer cells. Cytocompatibility was confirmed across all formulations, while confocal laser scanning microscopy revealed enhanced cellular association and internalization of CS-FA–coated nanoparticles in MDA-MB-231 cells, attributed to folate receptor–mediated interactions. In contrast, minimal nonspecific uptake was observed in iMEFs, indicating surface-selective behavior.

Overall, the study demonstrated how folic acid–functionalized chitosan coatings can be used to surface-engineer PLA-based nanoparticles with tunable interfacial properties and selective biological interactions. The findings highlight the potential of hybrid organic coatings to simultaneously optimize coating performance and enable targeted drug delivery functionalities within a safe and sustainable materials design framework.