Abstract
416
Objectives Presently, there are no effective treatments for several diseases involving CNS. The objective of this study was to investigate the delivery of prospective therapeutics and model macromolecules and nanoparticles after intrathecal lumbar (IT) administration.
Methods Four recombinant human enzymes, model polymers of various molecular weights, virions and synthetic and phage particles, were labeled with 124I and administered IT to rats and cynomolgus monkeys. Dynamic imaging data (0-20 min post injection) and multiple static images were acquired over at least 48 hours after the injections. Images were analyzed to determine the rate and patterns of the label spread in CSF from the injection site and further into CNS.
Results After the injection, all molecules and particles were distributed in the CSF. Deposition at the injection site did not exceed deposition elsewhere in the leptomeningeal compartment. Penetration into both white and gray matter as well as major nerves were found by 5 hours after the injection. Penetration to the systemic circulation was detected early after the injection, the data suggests non-lymphatic size-dependent direct drainage to the blood with CSF.
Conclusions The data suggest that IT administration of macromolecules and nanoparticles can be beneficial for the treatment of diseases involving CNS. The mechanisms and rates of macromolecule and particle clearance from CSF and penetration to the brain parenchyma require further investigation.
Research Support NIH R21CA152384. DoD USAMRMC BC100684, and grants from Shire HGT