Methods of Drug Delivery in Neurotrauma

Abstract

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.

Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis in Parkinson's disease models both in vitro and in vivo

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Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury

“…Acute intervention of oxidative stress processes could limit the negative effects of secondary injury mechanisms on TBI outcome. A challenge to TBI treatment, and the treatment of any central nervous system (CNS) disorder, is drug delivery to and across the BBB 21 . Notably, the endothelial cell layer that constitutes the luminal most component of the BBB represents an important therapeutic target in conditions involving oxidative stress and inflammation, such as TBI 22, 23 .…”

Techniques for Multiscale Neuronal Regulation via Therapeutic Materials and Drug Design

“…Although many possible drug treatments with specific cell-based mechanisms of actions have been identified to promote neural repair and alleviate chronic pain, often only a small amount of drug is actually delivered to the disease site . The effectiveness of such treatments is compromised due to poor pharmacokinetic profiles, substantial off-target toxicity, and limitations with the administration route. − Using chronic pain as an example, current therapeutics often rely on passive targeting, in which enhanced permeability at the injury site and spinal cord allow for extravasation of drugs into the CNS. , Yet, those agents are rapidly cleared from the blood and are not sufficiently delivered to the spinal cord where nociceptive processing occurs. Many chronic pain treatments in both human and animal studies have sought to improve efficacy by delivering therapies using intrathecal drug delivery systems. ,,− Intrathecal drug delivery systems administer drugs directly into the spinal canal allowing direct access to cerebrospinal fluid, which improves on-target delivery as well as lowers the effective dose of drug needed. , However, such delivery systems, including intrathecal injections, are highly invasive and can result in complications like bleeding and infection .…”