Abstract
Overcoming the challenge of effectively delivering drugs to the central nervous system (CNS) is crucial for treating various neurological disorders. The intrathecal (IT) approach, involving direct injection into the cerebrospinal fluid (CSF), bypasses the blood-brain barrier (BBB) and holds promise for addressing this challenge. However, the delivery strategies are yet undefined due to numerous factors affecting the solute transport in the intrathecal space. Animal experimentation is restricted due to ethical and economic concerns. In vitro modeling holds a unique advantage, serving as a bridge between pre-clinical and clinical studies. The current study presents the application of in vitro benchtop methods that are optimized to quantify the solute transport in both human and Non-Human Primate models. A range of injection and physiological parameters were evaluated to understand their impact on intrathecal solute transport. Additionally, the effect of cardiac and respiration-related CSF oscillations on solute transport was investigated. The findings of this research provide quantitative predictions on optimizing existing IT delivery protocols or designing pre-clinical studies.