Methods of Drug Delivery in Neurotrauma.
The central nervous system (CNS) is protected by blood-brain barrier (BBB) and blood-cerebrospinal-fluid (CSF) barrier that limit toxic agents and most molecules from penetrating the brain and spinal cord. However, these barriers also prevent most pharmaceuticals from entering into the CNS. Drug delivery to the CNS following neurotrauma is complicated. Although studies have shown BBB permeability increases in various TBI models, it remains as the key mitigating factor for delivering drugs into the CNS. The commonly used methods for drug delivery in preclinical neurotrauma studies include intraperitoneal, subcutaneous, intravenous, and intracerebroventricular delivery. It should be noted that for a drug to be successfully translated into the clinic, it needs to be administered preclinically as it would be anticipated to be administered to patients. And this likely leads to better dose selection of the drug, as well as recognition of any possible side effects, prior to transition into a clinical trial. Additionally, novel approach that is noninvasive and yet circumvents BBB, such as drug delivery through nerve pathways innervating the nasal passages, needs to be investigated in animal models, as it may provide a viable drug delivery method for patients who sustain mild CNS injury or require chronic treatments. Therefore, the focus of this chapter is to present rationales and methods for delivering drugs by IV infusion via the jugular vein, and intranasally in preclinical studies.
Brain Trauma Neuroprotection and Neurorestoration Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, USA. ying.d.bryant.civ@mail.mil.
Ying
Y
Deng-Bryant
Brain Trauma Neuroprotection and Neurorestoration Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, USA.
Ryan
R
Readnower
Brain Trauma Neuroprotection and Neurorestoration Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, USA.
Lai Yee
LY
Leung
Brain Trauma Neuroprotection and Neurorestoration Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, USA.
Frank
F
Tortella
Brain Trauma Neuroprotection and Neurorestoration Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, USA.
Deborah
D
Shear
D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D051381:Rats; D020196:Trauma, Nervous System / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D004364:Pharmaceutical Preparations
Drug delivery; Intranasal; Intravenous; Neurotrauma; Traumatic brain injury