Design Evolution of Curcumin-Loaded Nanostructured Lipid Carriers: Formulation Strategies, Functional Modifications, and Mechanistic-Translational Perspectives.

Curcumin possesses broad therapeutic potential but remains severely limited by poor solubility, instability, and low systemic bioavailability. Nanostructured lipid carriers (NLCs) have emerged as an advanced lipid-based delivery platform capable of overcoming these constraints through optimized lipid organization, high drug-loading capacity, and tunable surface functionality. This review provides a comprehensive examination of the design evolution of curcumin-loaded NLCs (Cur-NLCs), encompassing core components, formulation strategies, preparation techniques, and quality determinants that govern physicochemical and biological performance. Evidence-based classification of formulation approaches is presented, highlighting single-drug, co-loaded, and surface-modified or functionally engineered NLC systems and their respective therapeutic advantages. Mechanistic insights are discussed to elucidate how NLCs enhance curcumin's stability, absorption, intracellular trafficking, and controlled release. Current challenges, including formulation heterogeneity, scalability, long-term stability, and translational readiness, are critically evaluated, alongside emerging clinical observations from engineered NLCs that further underscore their translational relevance. From a translational standpoint, the review identifies NLC designs based on pharmaceutically accepted lipids, scalable preparation methods, and minimal surface complexity as the most feasible candidates for near-term clinical development, while more elaborate multifunctional or ligand-modified systems are discussed as promising but longer-term strategies. However, the progress outlined in this review highlights NLCs as a highly adaptable platform capable of unlocking curcumin's full pharmacological potential and accelerating its pathway toward therapeutic applicability.