Delivery of Therapeutic Plant-Derived Exosomes to the Brain for the Treatment of Mental Health Disorders and CNS Injuries

N. NassiriKoopaei
EriVan Bio and University of Florida,
United States

Keywords: targeted drug delivery, brain, exosomes


Mental health, traumatic brain injuries [TBI], and addictive disorders affect more than 1 billion people globally and are expected to cost the world economy well over $6 trillion by 2030. Within this space, disorders such as treatment-resistant depression, TBI, and post-traumatic stress disorder [PTSD] are inadequately treated, resulting in chronic disorders, and increased individual suffering. The Veterans Administration reported 16.8 veteran suicides per day in 2020, but a 2022 study from America’s Warrior Partnership, discovered that thousands of cases of suspected or confirmed suicides were not included in federal calculations. To address these alarming numbers and debilitating disease conditions arising from service to country, EriVan Bio is developing a next generation natural nanoparticle delivery system for cannabinoids and other drug compounds, using exosomes. Exosomes, a type of extracellular vesicle [EV], are nanoscale membrane-enclosed lipid particles implicated in intercellular communication by facilitating the transport of proteins and genetic material. Cannabinoids have long been used for their remedy of different ailments such as pain, seizures, chemotherapy associated symptoms, and for their direct anti-inflammatory activity. For central nervous system [CNS] therapeutic purposes, crossing the blood-brain barrier [BBB] to reach the brain and to obtain therapeutic concentrations, patients are required to consume relatively high doses of cannabinoids orally daily. If cannabinoids are taken orally, they undergo extensive hepatic first-pass metabolism which reduces their plasma concentration and increases the psychoactive metabolite, 11-hydroxy THC. Furthermore, administration of low doses to avoid psychoactive effects of THC may result in a suboptimal concentration in the CNS that may not significantly improve the patient’s disease state. To avoid these problems in CNS therapy, cannabinoids may be delivered intracranially, which is an invasive and traumatic procedure. At EriVan Bio our innovative approach is the nano-packaging of one or more cannabinoids into hemp-derived exosomes which employs a targeted and noninvasive intranasal delivery strategy to cross the BBB. This delivery platform reduces the overall administered dose of cannabinoids and their undesirable side effects, while maintaining cannabinoids effects on CNS disorders and TBI. Given the ability to both bioengineer the hemp plant for enriched production of certain cannabinoids or harvest EVs from different hemp cultivars, plant-derived exosomes provide a cannabinoid delivery system that can be used to treat conditions such as concussion, TBI, PTSD, and degenerative diseases. Within EriVan’s pipeline of exosome-based products we can isolate exosomes from different sources, load the natural nanoparticles with drugs, and delivery these across the BBB via intranasal delivery. We demonstrated that plant EVs are more efficient vectors than other methods of delivery indicating an improvement of intranasal delivery efficacy and oral delivery when using plant EVs. Therefore, intranasal delivery of drugs using plant and/or stem cell-derived exosomes is feasible and provides a direct and better-controlled approach to get drugs into the brain. The large unmet need in the mental health space is the initial clinical direction for EriVan, with a focus on providing a better delivery system for treating conditions such as PTSD and TBI.