Hemp proteins conjugated with green tea polyphenol extract form de novo plant-sourced emulsifiers suitable for nanodelivery systems bearing lipophilic psychopharmaceuticals

Nanoformulation is often used to improve the solubility and uptake of bioactives; however, it also protects sensitive bioactives from chemical decomposition. We report a class of biocompatible emulsifiers created by conjugating hemp protein with green tea polyphenols. A simple pH-assisted coupling protocol was employed to synthesize covalent and non-covalent conjugates, which were then used to produce 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enriched hemp oil nanoemulsions in water with an average droplet sizes of ca. 200 nm and ζ potential values of ca. -40 mV. Our de novo emulsifiers protected the sensitive drug under conditions of simulated oxidative stress, an indication that the antioxidant properties of polyphenols are retained. These emulsions were resistant to a wide variety of emulsion-breaking stressors and demonstrated remarkable colloidal stability over a period of 4 weeks with no evidence of phase separation. Fluorescence and confocal imaging confirmed cellular uptake of the formulation, while in vitro cytotoxicity assays showed acceptable cell viability with drug-loaded nanoemulsions. This represents an ingestible 5-MeO-DMT formulation; the sensitivity of this molecule mandates some form of formulation for reasonable bioavailability and reproducible dosages.