Date of Award
ABSTRACT JASON BLAKE PRICE: Surface-Eroding Drug Delivery Films for Sequential and/or
Intermittent Release of Psychoactive Drugs For patients with psychiatric diseases, adherence to medication schedules, medication
errors, and abuse are common issues. Promising new forms of therapy for these patients, such as micro-dosed lysergic acid diethylamide (LSD), where patients receive 10-20% of a full dose every third day, present further drug delivery challenges. Sequential or intermittent release of drugs from an implanted device could ensure long-term drug compliance, automate drug dosing during the life of the implant, and eliminate potential for abuse and medication errors. To this end, we generated polymeric films composed of cellulose acetate phthalate (CAP) and Pluronic F-127 (P) polymers that can co-encapsulate a wide variety of drug molecules. We generated CAPP films via a slow solvent evaporation method, where CAP and P were dissolved – along with one of two model drugs Fluorescein or Rhodamine B– in acetone and left to dry at 4 degrees Celsius. The films slowly re-dissolve in Phosphate-buffered saline (PBS) via surface erosion to allow controlled drug release. Single layer CAPP films were eroded using 300, 600, 900, 1200, 1600, and 1800 mg polymer mass groups to study the relationship between polymer thickness and erosion rate. Based off that analysis, polymer thickness and erosion rate had a positive correlation that increased linearly. Drug release profiles were quantified from single layer devices to establish the connection between film thickness and drug concentration release. Based off release profiles generated from the analysis of single layer devices, multilayered devices were fabricated to achieve controlled, intermittent release of the model drugs. We found that the multilayered devices could successfully release Fluorescein and Rhodamine B in a sequential and/or intermittent order with a delay of 48- 72 hours between release. To further tailor the films, polymer concentration, layer order, and
encapsulated drugs can be varied in a modular manner. Thus, CAPP films are a promising technology for long-term, sequential and/or intermittent release of psychiatric agents from an implantable device, and the device will be further optimized to achieve ideal release profiles for the micro-dosing of LSD in patients with treatment-resistant depression.
Price, Jason, "Surface-Eroding Drug Delivery Films for Sequential and/or Intermittent Release of Psychoactive Drugs" (2021). Honors Theses. 1751.
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