Innovations in Nanobot and Microbot Propulsion for Targeted CNS Drug Delivery Across the Blood–Brain Barrier

The transport of therapeutic molecules to the brain is one of the largest challenges of contemporary medicine because of the restrictive nature of the blood-brain barrier (BBB), which blocks the penetration of almost all biological therapeutics and most small-molecule drugs. This is a major limitation to the treatment of such neurological diseases as Parkinson's disease (PD), glioblastoma, and Alzheimer's disease. To beat these obstacles, there must be advanced delivery systems that can be precise, be released under control, and move without being invasive. Over the past decade, there have been innovations in micro and nanorobotic technologies, which provide a groundbreaking model that incorporates innovations in materials science, analytical chemistry, and biomedical engineering. Such engineered nanorobots are magnetically controlled, polymeric, or biologically derived nanorobots, which can be magnetically, acoustically, optically, or chemically controlled, and can cross the BBB with greater specificity. It has also been possible to follow the behavior of nanorobots at a direct visualization level in biological systems due to the development of analytical tools, especially imaging, real-time monitoring, and in situ sensing, which allows the behavior of nanorobots to be evaluated rigorously in terms of motions, shape transformation, and drug release profiles. The present review gives a detailed description of the propulsion-based nanorobotic drug delivery systems to the central nervous system (CNS), including structural components, modes of actuation, and protocols of analysis. The review explains that the combined effects of physicochemical features, external stimuli, and interactions between biointerfaces influence permeability via the BBB and accuracy of therapeutic response.