Optimizing oil selection for curcumin-based nanoemulsions formulation through molecular self-assembly

Curcumin is a bioactive compound with anti-inflammatory and anticancer activity, which is poorly water solubility and stability that limiting its therapeutic potential. Curcumin delivery can be improved by oil-in-water nanoemulsions by providing a hydrophobic core, but it is challenging to develop stable systems due to oil-drug compatibility. Molecular dynamics simulations were used to compare two oil cores of linoleic acid (LA) from safflower oil and oleyl laurate (OL) from palm kernel oil esters for curcumin nanoemulsions. The LA structure exhibited smaller structural movements, reduced radius of gyration (Rg) and more persistent intermolecular hydrogen bonds than the OL system. The higher number of CC-LA hydrogen bonds suggest the curcumin molecules become more densely packed with LA to form a tightly ordered hydrophobic core with its amphiphilic character enables a closely packed self-assembly with curcumin. Based on these findings, an optimized nanoemulsion was formulated by adding lecithin (LC) and Tween 85 (T85) into CC-LA (CC-LA-LC-T85), with LC and T85 appearing to enhance the aggregation rate. In simulations, self-association of surfactants occurred at the droplet interface with exposed polar head groups, a uniform shell around a CC-LA core. The ultimate aggregate was near-spherical and structurally hard, as shown by a stable Rg and minimal molecular diffusion. The dense hydrophobic core formed by LA, stabilized by persistent interactions with LC and T85, demonstrated a compact and organised self-assembled structure. These intermolecular interactions collectively ensured effective encapsulation and well-defined nanoemulsion, rendering its potential suitability as a carrier for future curcumin encapsulation in drug delivery applications.