Intranasal delivery of drug-loaded polymeric nanomicelles for brain targeting: a comprehensive review

Brain disorders affect over one-third of the global population, representing a major therapeutic challenge. Physiological barriers like the blood–brain barrier, intestinal barrier, and the cerebrospinal fluid barrier are the major obstacles for drugs to penetrate into the brain. Developing novel strategies to enhance the delivery of drugs to the brain has become a major focus in pharmaceutical research and development. The nasal route of drug delivery in conjunction with nanoparticles has shown great potential for the management of brain disorders due to the direct linkage of the nasal route to the brain through olfactory and trigeminal nerves. Nanomicelles have been found to be a potential carrier system for improving the brain concentrations of a variety of drugs. In most of the published works, the size range of polymeric nanomicelles for brain targeting through the nasal route was identified to be between 30 and 150 nm. This review focuses on the important aspects of nose-to-brain delivery, types of micelles, preparation methods, and characterization techniques. Further, drug-loaded polymeric nanomicelles for brain diseases through the nasal route have been explored critically with emphasis on the physicochemical characteristics, in vitro findings, and in vivo studies. Subsequently, marketed products, clinical trials (19 studies were reviewed), and patent reports are also presented. In the end, the challenges faced in developing micelles and their future prospects were also discussed. It was concluded that the polymeric nanomicelles delivered via the nasal route showed a high clinical translational potential for the management of brain diseases.

Graphical Abstract