Title : Novel nano drug platform for pharmacologically inducing therapeutic hypothermia (TH) after traumatic brain injury (TBI)
Abstract:
Therapeutic hypothermia (TH) has gained widespread recognition as a neuroprotective strategy for mitigating secondary injury mechanisms resulting from traumatic brain injury (TBI). TBI occurs when an external force impacts the skull, causing damage to the brain. TH modulates neuropathological responses caused by TBI. Our approach utilizes intranasal delivery of nanoscale vanilloid drugs, specifically olvanil, to induce brain hypothermia through the activation of the transient receptor potential vanilloid 1 (TRPV1). Through a bottom-up synthesis, we prepared nanoolvanil, demonstrating its ability to bind to TRPV1 and activate the receptor, as evidenced by calcium influx assays. Toxicity studies revealed minimal impact on cell proliferation and indicated antioxidant effects in vitro. In vivo experiments employed a custom 3D-printed intranasal spray (INS) to deliver nanoolvanil.
Characterized by dynamic light scattering (DLS), nanoolvanil exhibited an average size of 82.53 nm, a polydispersity index (PDI) of 0.25, and a zeta potential of -28.05 mV—suitable for blood-brain barrier transport. TRPV1 activation studies showed a 34% calcium influx post-injection and nanoolvanil significantly increased cell proliferation. In vivo, the 3D-printed INS successfully delivered nanoolvanil at 5 mg/kg, leading to a temperature reduction of ~2 ? for up to 100 minutes. Nanoolvanil, falling within the optimal size range, effectively activated TRPV1 with minimal impact on cells. In vivo studies using our customized 3D-printed INS demonstrated successful head and body temperature reduction, highlighting the potential of this nanodrug delivery system for therapeutic hypothermia in TBI cases.
Audience Take Away Notes:
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Learn the thermoregulatory role of capsaicin
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Learn about therapeutic hypothermia approaches
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Learn the advantages of formulating therapies in the nanoscale
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This novel platform may boost scientific practices in other areas
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The delivery system may apply to other drugs