Engineered Commensals as Next-Generation Drug Delivery Agents for Nose-to-Brain Therapeutics in Neurological Disorders.

Central nervous system (CNS) disorders such as Alzheimer's diseases, Parkinson's diseases, stroke, and glioma remain among the most challenging to treat, largely due to the restrictive nature of the blood-brain barrier (BBB). In recent years, intranasal administration has emerged as a noninvasive route for CNS drug delivery. Due to its anatomical advantage over the traditional route, the nose-to-brain route can easily bypass the BBB and deliver drugs directly to the brain. Parallel advances in the interface of synthetic biology and materials engineering have led to the development of engineered living materials (ELMs) dynamic structures that embed mammalian cells, bacteria, or viruses within self-renewing or engineered matrices. These bioengineered systems have been developed as next-generation therapeutic platforms for various biomedical applications, utilizing intrinsic or engineered capabilities such as disease-targeted migration, localized therapeutic production, adaptive delivery, immune activation, and metabolic regulation. Therefore, developing a bioengineered commensal based delivery system that uses the intranasal route to effectively deliver drug across the BBB could represent a transformative strategy for treating CNS disorder and advancing neurotherapeutic research.