Octavio E Fandino, Aaron R J Hutton, Chunyang Zhang, Marco T A Abbate, Yara A Naser, Yaocun Li, Alejandro J Paredes, Ryan F Donnelly
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引用次数: 0
Abstract
Throughout history, psychedelic compounds have been used for religious, spiritual and recreational purposes. A plethora of studies have reported the use of psychedelic compounds in the treatment of various conditions, such as alcoholism, addictions, depressive state to borderline schizophrenia, personality disorder, among other mental disorders. Psychedelic microdosing, a common technique in recent years, involves the consumption of small doses of psychedelic drugs for therapeutic purposes. This study investigated the potential of hydrogel-forming microarray patches (HF-MAPs) to deliver N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and mescaline (MES) in small doses through the skin. To this purpose, HF-MAPs were prepared using poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP), using citric acid as the crosslinker. Two different reservoirs, containing PVP and PVA as the main components and poly(ethylene)glycol 400 (PEG400) and glycerol as plasticising agents, were used to deliver all the drugs from the HF-MAPs. Franz cells studies in excised neonatal porcine skin demonstrated that the permeation of DMT, 5-MeO-DMT and MES was better from the PEG400 reservoir, showing a permeation of 60.71 %, 59.61 % and 41.85 % respectively. Pharmacokinetic studies in rats showed that HF-MAP technology as a strategy for microdosing psychedelic compounds was also demonstrated with DMT. AUCt0-final for the HF-MAP cohort (7186 ± 1296 ng/mL*h) was significantly greater than the IM cohort (1803 ± 53.25 ng/mL*h) (p = 0.0020), with a relative bioavailability of ∼ 72 %. Considering their pharmacokinetic profile, the frequency of DMT dosing could be reduced with HF-MAP when compared to the IM route.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.