Hemp proteins conjugated with green tea polyphenol extract form de novo plant-sourced emulsifiers suitable for nanodelivery systems bearing lipophilic psychopharmaceuticals
William Charles Hosie, Mary Augustina Egbuta, Kasra Razmkhah, Behzad Bolandi, Khalilalrahman Dehvari, Anton A. Homon, Aleena Kappadakunnel, Jonathan J. Simone, Abhinandan Banerjee, John F. Trant
ChemRxiv February 27, 2025 DOI: 10.26434/chemrxiv-2025-pjfn9 via OpenAlex
Summary
AI-generated from the abstractA new class of biocompatible emulsifiers was created by conjugating hemp protein with green tea polyphenols using a simple pH-assisted coupling protocol. These emulsifiers were used to produce hemp oil nanoemulsions enriched with 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), achieving average droplet sizes of about 200 nm and ζ potential values of about -40 mV. The polyphenol-conjugated emulsifiers protected the sensitive drug under simulated oxidative stress, indicating retained antioxidant properties. The emulsions resisted various stressors and showed colloidal stability for 4 weeks without phase separation. Cellular uptake was confirmed by imaging, and in vitro cytotoxicity assays showed acceptable cell viability with drug-loaded nanoemulsions, offering an ingestible formulation for improved bioavailability of 5-MeO-DMT.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Interventions | 5-methoxy-N N-dimethyltryptamine (5-MeO-DMT) enriched hemp oil nanoemulsion |
| Duration | 4 weeks |
| Keywords | Polyphenol Chemistry Green tea Conjugated system Traditional medicine |
| Key finding | Hemp protein–green tea polyphenol conjugates serve as effective emulsifiers for producing stable, ingestible nanoemulsions of 5-MeO-DMT that protect the drug from oxidative stress and show acceptable cell viability. |
Abstract
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.