Intracalvariosseous administration of donepezil microspheres protects against cognitive impairment by virtue of long-lasting brain exposure in mice

Recent studies have demonstrated the direct connections between the skull bone marrow, meninges, and brain. In an effort to explore these connections for the purpose of brain drug delivery, we previously proposed the direct application of CNS drugs into the diploic space between the outer and inner cortex of the skull, namely, intracalvariosseous administration (ICO). It was successfully demonstrated that small molecular to large colloidal drugs can readily reach the brain after ICO in mice and rabbits. Here, we report that a single ICO of donepezil microspheres protects cognitive impairment in Alzheimer mouse models over a month-long period.