Interval delivery of 5HT_2A agonists using multilayered polymer films

Area of Science:

• Neuroscience
• Pharmacology
• Biomaterials Science

Background:

• Treatment-resistant depression (TRD) affects approximately 50% of depression patients, posing a significant unmet medical need.
• Classical psychedelics, specifically 5HT2A agonists, are emerging as a promising therapeutic avenue for TRD.
• Current challenges in psychedelic therapy include dosing compliance, substance diversion, and administration costs, particularly for microdosing regimens.

Purpose of the Study:

• To develop an innovative drug delivery system for the controlled, interval release of 5HT2A agonists.
• To overcome practical barriers associated with psychedelic microdosing for TRD treatment.
• To investigate the feasibility of biodegradable implants for sustained psychedelic delivery.

Main Methods:

• Development of multilayered cellulose acetate phthalate (CAP)/Pluronic F-127 (P) films for encapsulation.
• Optimization of CAPP film composition, thickness, and layering for controlled release.
• In vitro demonstration of three distinct release pulses and in vivo pharmacokinetic/biodistribution studies of 2,5-Dimethoxy-4-iodoamphetamine (DOI) via subcutaneous implants.

Main Results:

• Successfully developed and optimized multilayered CAPP films capable of interval drug delivery.
• Demonstrated three distinct release pulses from the CAPP films in vitro.
• Quantified the pharmacokinetics and biodistribution of DOI following subcutaneous implantation of CAPP films, confirming sustained release.

Conclusions:

• This study presents the first implantable drug delivery system for the interval delivery of psychedelics.
• The developed system offers a potential solution to improve compliance and manage dosing for psychedelic microtherapies.
• This innovation paves the way for future research into the therapeutic potential of precisely delivered psychedelics for depression.