Three Dimensional Simulation and Experimental Investigation of Intrathecal Drug Delivery in the Spinal Canal and the Brain

摘要

Intrathecal drug delivery bypasses the blood brain barrier by infusing therapeutic agents into the cerebrospinal fluid. Clinical studies have observed rapid distribution of intrathecally infused drugs. We hypothesize that naturally occurring cerebrospinal fluid pulsations inside the spinal canal accelerate drug transport. An experimental model of the human spinal canal was built for infusion tests of a radionucleotide in stagnant and pulsatile flow fields. The distribution of infused Technitium-99m in the spinal canal model was quantified and validated with computational study. The results show that the oscillatory flow of the cerebrospinal fluid accelerates species dispersion in the spinal canal model by a factor of two to four. To demonstrate a clinically relevant application, physiological cerebrospinal fluid pulsations were reproduced in an anatomically consistent computational model and the dispersion of baclofen, an anti-spasticity drug, inside the central nervous system was predicted. The successful characterization of accelerated drug transport due to cerebrospinal fluid pulsations aids in the rational design of intrathecal drug infusion therapies.