Morris, Jodie, Letson, Hayley, and Dobson, Geoffrey (2024) Safety evaluation of adenosine, lidocaine and magnesium (ALM) intranasal therapy toward human nasal epithelial cells in vitro. Basic and Clinical Pharmacology and Toxicology. (In Press)

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Abstract

Adenosine, lidocaine and Mg2+ (ALM) solution is an emerging therapy that reduces secondary injury after intravenous administration in experimental models of traumatic brain injury (TBI). Intranasal delivery of ALM may offer an alternative route for rapid, point-of-care management of TBI. As a preliminary safety screen, we evaluated whether ALM exerts cytotoxic or inflammatory effects on primary human nasal epithelial cells (pHNEC) in vitro. Submerged monolayers and air–liquid interface cultures of pHNEC were exposed to media only, normal saline only, therapeutic ALM or supratherapeutic ALM for 15 or 60 min. Safety was measured through viability, cytotoxicity, apoptosis, cellular and mitochondrial stress, and inflammatory mediator secretion assays. No differences were found in viability or cytotoxicity in cultures exposed to saline or ALM for up to 60 min, with no evidence of apoptosis after exposure to supratherapeutic ALM concentrations. Despite comparable inflammatory cytokine secretion profiles and mitochondrial activity, cellular stress responses were significantly lower in cultures exposed to ALM than saline. In summary, data show ALM therapy has neither adverse toxic nor inflammatory effects on human nasal epithelial cells, setting the stage for in vivo toxicity studies and possible clinical translation of intranasal ALM therapy for TBI treatment.

Item ID:	82882
Item Type:	Article (Research - C1)
ISSN:	1742-7843
Keywords:	ALM therapy, cytotoxicity, intranasal administration, nasal epithelium, safety, traumatic brain injury
Copyright Information:	© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Funders:	College of Medicine and Dentistry, James Cook University (JCU)
Date Deposited:	27 May 2024 05:23
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3208 Medical physiology > 320801 Cell physiology @ 30% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321407 Toxicology (incl. clinical toxicology) @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320907 Sensory systems @ 20%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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