Mechanistic insights into nanostructured lipid carriers: from lipid architecture to drug release behavior

Nanostructured lipid carriers (NLCs) are advanced lipid-based nanocarriers. They were developed to overcome the limitations associated with solid lipid nanoparticles (SLNs). Traditional SLNs often face problems such as the risk of drug expulsion during storage and low drug loading due to lipid crystallization. NLCs incorporate a combination of solid and liquid lipids in their matrix, with surfactants used to stabilize the particles. This combination creates a less ordered structure with small imperfections in the matrix, which can improve drug loading and reduce drug expulsion. Relevant literature was searched in PubMed, Google Scholar, Scopus, and Web of Science for publications from 2021 to 2026. This review focuses on how the design of the lipid matrix influences the performance of NLCs. The paper also discusses important physicochemical factors such as partitioning behavior and drug solubility in lipids, which play a key role in drug-lipid interactions. In addition, the relationship between formulation variables, lipid matrix organization, and overall performance is explained. A better understanding of these relationships, along with the mechanisms involved in drug absorption, can support the rational design of NLC formulations. The aim is to help researchers develop lipid-based nanocarriers that are more stable and effective for different drug delivery applications.