Synthesis and Application of Nanovanilloids for Localized Therapeutic Hypothermia after Traumatic Brain Injury

Vanilloids are natural and synthetic compounds with cooling properties that are highly hydrophobic, which impede their use in biomedical applications. To overcome this challenge, we synthesized nanodrugs from hydrophobic vanilloids using modified reprecipitation that yields monodisperse nanoparticles with long-term stability. Cooling or therapeutic hypothermia (TH) is used to lower body temperature in acute injury to protect organs or neurons in the brain from damage. Currently, cooling can only be performed in hospitals and not at the location site of injury or during transport, limiting its effectiveness. To address this need, synthesized vanilloid nanodrugs were incorporated into formulations for nasal delivery to allow the nanodrug materials to reach and cool the brain rapidly. The physicochemical characteristics and cooling properties of vanilloid nanomaterials were determined. Feasibility of intranasal nanovanilloid delivery was demonstrated in a rat traumatic brain injury model using an in-house-3D-printed intranasal device where nanorinvanil and nanoolvanil produced rapid, sustained brain cooling (-3.6 °C and -2.0 °C, respectively, for over 90 min). This highlights the potential of this method for harnessing the innate cooling properties of vanilloid compounds that are too hydrophobic for use through synthesis of nanodrugs that enable material formulations with optimal characteristics for achieving therapeutic hypothermia.