In silico and in vitro profiling of sphingomyelin loaded zein nanoconstructs with optimized aromatic interactions and...

To enhance therapeutic efficacy and achieve controlled drug release for colon cancer therapeutics, this study focuses on developing a hydrocolloid-based, pH-responsive biocompatible nanocarrier. We synthesized sphingomyelin (SM)-loaded zein nanoparticles (SM-LNPs) stabilized using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), leveraging the aromatic interactions of zein to optimize drug encapsulation and release kinetics. In silico molecular docking and molecular dynamics (MD) simulations demonstrated strong intermolecular interactions between zein, SM, and EDC, supporting the formulation's rational design. Comprehensive physicochemical characterization confirmed the stability and structural integrity of SM-LNPs. Dynamic light scattering (DLS) and field emission scanning electron microscopy (FE-SEM) analyses revealed a monodispersed, spherical morphology with an optimized particle size suitable for oral drug delivery. In vitro drug release studies indicated a sustained and pH-responsive release profile, with 90.60 % of SM released at pH 6.8, mimicking intestinal conditions. Cell viability assays using HCT 116 colon cancer cells showed that SM-LNPs exhibited significantly enhanced cytotoxicity (41.44 % reduction in cell viability) compared to free SM, confirming their potential for cancer therapeutics. Additionally, pharmacokinetic simulations validated the controlled release and systemic retention of SM, supporting its suitability for oral administration. Our findings demonstrate that SM-LNPs offer a promising drug delivery platform with enhanced stability, pH response release, and improved bioactivity, paving the way for their potential application in colon cancer treatment. This research provides critical insights into nanocarrier design, drug delivery kinetics, and biomaterial-based therapeutic strategies for precision oncology.