The reported research revealed the peculiarity of stimuli-responsive lipidic nanocarriers for localised therapy in distinct brain diseases, as it is supremely challenging due to the complexity of the brain. The pitfalls of conventional carriers could be carefully addressed utilising these smart lipidic nanoparticles due to their versatile features. The meticulous depiction of cardinal strategies for boosting barrier penetration with a mechanism paves the roadmap for lipidic nanoparticles in targeting. The present review article offers viewpoints on the application of distinct endogenous stimuli, like pH, hypoxia, and enzymes, along with exogenous stimuli, such as temperature, magnetism, and light. Each stimulus elaborated their exploitation of pathophysiological changes during diseased conditions, and its mechanism of utilisation in treating the diseases protects healthy cells from damage. Importantly, the detailed emphasis on the role of lipidic nanocarriers and their key advantages, including biosafety, biocompatibility, and high payload, offers a new avenue for targeted therapies. The stimuli-responsive lipid-nanoparticle-mediated targeted therapy in conditions like neurodegenerative diseases (Alzheimer's and Parkinson's), tumours like glioblastoma multiforme (GBM), infectious conditions like meningitis, and traumatic conditions like intracerebral haemorrhage are discussed in this work. Despite advancements, fewer issues like nanotoxicity, controlled size, scalability, and distribution within the brain appear to have more solutions. In future multi-stimuli applications, biomolecule integration and clinical translation could resolve many of the drawbacks of the present situation. Concisely, in the future, stimuli-responsive lipid nanoparticles will serve as an intriguing approach for targeted therapy in brain diseases.
