Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain.
Several treatment modalities for neurodegenerative diseases or tumors of the central nervous system involve invasive delivery of large molecular weight drugs to the brain. Despite the ample record of experimental studies, accurate drug targeting for the human brain remains a challenge. This paper proposes a systematic design method of administering drugs to specific locations in the human brain based on first principles transport in porous media. The proposed mathematical framework predicts achievable treatment volumes in target regions as a function of brain anatomy and infusion catheter position. A systematic procedure to determine the optimal infusion and catheter design parameters that maximize the penetration depth and volumes of distribution will be discussed. The computer simulations are validated with agarose gel phantom experiments and rat data. The rigorous computational approach will allow physicians and scientists to better plan the administration of therapeutic drugs to the central nervous system.
Linninger
Andreas A
AA
Laboratory for Product and Process Design, Department of Chemical and Bioengineering, University of Illinois, Chicago, IL 60607, USA. linninge@uic.edu
Somayaji
Mahadevabharath R
MR
Zhang
Libin
L
Smitha Hariharan
Madhu
M
Penn
Richard D
RD
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D003198:Computer Simulation; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008956:Models, Chemical; D008959:Models, Neurological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010599:Pharmacokinetics; D016062:Porosity; D051381:Rats
D046911:Macromolecular Substances; D004364:Pharmaceutical Preparations