Towards digital transformation: A Quality by Design approach to plant-based nanostructured lipid carriers formulation.

This study establishes a streamlined, scalable, and reproducible workflow for the sustainable and computationally guided development of nanostructured lipid carriers (NLCs) by integrating Quality by Design and molecular simulations with sustainable approaches in formulating plant-based NLCs loaded with curcumin (CUR) as a model natural molecule. Our approach aims to accelerate the screening, optimization, and development processes of nanoformulations while maintaining drug loading and stability and adhering to green chemistry principles. A combined-mixture process and a 3 Factorial/RSM experimental design were used. NLCs were prepared using high-shear hot homogenization at 12,000 RPM for 10 min. Following characterization, NLCs were optimized and evaluated. Molecular dynamics simulations were conducted using GROMACS to study the interaction between CUR and NLCs. The optimized CUR-NLCs had a particle size (80.28 - 87.31 nm), PDI (0.239 - 0.276), and Zeta potential (-11.63 to -14.67 mV), with an encapsulation efficiency (53 - 63 %). The optimized CUR-NLCs demonstrated desirable properties while using plant-based materials and sustainable methods. Employing molecular simulations provided insights into the assembly of NLCs and CUR interactions with their components. The proof-of-concept successfully bridged process optimization with advanced computational pharmaceutics, ensuring that digital transformation and sustainability are at the core of future nanoformulation research and industrial adoption.