Incorporation of a Natural Deep Eutectic Solvent-Based System as a Cryoprotectant in Solid Lipid Nanoparticles: Advancing toward Industrial Scalability.

The industrial-scale production of solid lipid nanoparticles (SLNs) faces significant challenges, such as degradation during freezing and the reliance on toxic solvents for cryoprotection and active ingredient solubility, hindering their effective storage and commercialization. This study presents an innovative and sustainable approach to SLNs formulation by incorporating a natural deep eutectic solvent-based system (NaDES) as an integral part of the system. The research evaluated the cryoprotective potential of NaDES at different concentrations and freezing methods, demonstrating their ability to stabilize aluminum chloride phthalocyanine (AlClPc)-loaded SLNs during freezing and enable drying protocols to enhance particle concentration. SLNs formulations with high colloidal stability were obtained, containing 12.5% NaDES, based on low-energy methodologies and high added value. Additionally, the use of NaDES enabled a 12.5% reduction in the water content in the formulation and acted as an efficient cryoprotectant, allowing for the freezing of SLNs without compromising particle integrity. These advancements suggest a greener and potentially scalable methodology for SLNs production, positioning NaDESs as promising cryoprotectants that may enhance formulation stability, improve commercial viability, and reduce production and storage costs. This innovation may represent an initial step toward improving nanoparticle preservation and facilitating future industrial translation, with the potential to broaden nanoparticle application in nanotechnology.