Self-nanoemulsifying drug delivery systems (SNEDDS) as psychotherapeutic couriers

Abstract

Clinical trials of psychedelics have shown preliminary promise for the treatment of psychiatric conditions such as major depressive disorder, substance use disorder, and treatment resistant depression.The most common psychedelic administration routes explored so far include intravenous injection, heated vapor inhalation, or a simple buffered salt solution administered to the nasal cavity.Given the treatment burden and person-to-person variance in bioavailability associated with these routes, it remains uncertain if they are viable for controlled therapy.Herein, we present a novel psychedelic nanoformulation -a self-nanoemulsifying drug delivery system -containing 5-MeO-DMT (SNEDDS-5M), a potent psychedelic being studied clinically, as payload.The self-nano-emulsifying properties of the system are attributed to Kolliphor HS15 (macrogol 15 hydroxystearate), a nonionic pharmaceutical surfactant and solubilizer.The formulation was further modified by the addition of α-tocopherol, a lipophilic antioxidant, to enhance the in situ stability of the encapsulated drug.While initially designed for oral ingestion, we have further customized the delivery system for intranasal administration.Upon hydration of the SNEDDS-5M, the lipid nanodroplets bearing the drug show an average droplet size of ca. 30 nm and a PDI of ca.0.06 while retaining pH dependent drug release.The nanoemulsion was readily amenable to increased drug loading and dissolution into a nasal spray formulation Finally, we show that the formulations are non-toxic at therapeutic concentrations.