Progress and perspectives of brain-targeting lipid-based nanosystems via the nasal route in Alzheimer's disease

Since health care systems dedicate substantial resources to Alzheimer's disease (AD), it poses an increasing challenge to scientists and health care providers worldwide, especially that many decades of research in the medical field revealed no optimal effective treatment for this disease. The intranasal administration route seems to be a preferable route of anti-AD drug delivery over the oral one as it demonstrates an ability to overcome the related obstacles reflected in low bioavailability, limited brain exposure and undesired pharmacokinetics or side effects. This delivery route can bypass the systemic circulation through the intraneuronal and extraneuronal pathways, providing truly needleless and direct brain drug delivery of the therapeutics due to its large surface area, porous endothelial membrane, the avoidance of the first-pass metabolism, and ready accessibility. Among the different nano-carrier systems developed, lipid-based nanosystems have become increasingly popular and have proven to be effective in managing the common symptoms of AD when administered via the nose-to-brain delivery route, which provides an answer to circumventing the BBB. The design of such lipid-based nanocarriers could be challenging since many factors can contribute to the quality of the final product. Hence, according to the authors, it is recommended to follow the quality by design methodology from the early stage of development to ensure high product quality while saving efforts and costs. This review article aims to draw attention to the up-to-date findings in the field of lipid-based nanosystems and the potential role of developing such forms in the management of AD by means of the nose-to-brain delivery route, in addition to highlighting the significant role of applying QbD methodology in this development.