Developing biodegradable long acting drug delivery systems for the treatment of chronic conditions

Abstract

Implantable drug delivery systems could be considered an alternative therapeutic option for chronic conditions such as cancer, cardiovascular diseases, diabetes, chronic respiratory diseases, and mental health disorders, among others. These systems can improve dosing regimens and patient adherence to treatment by eliminating the need for daily and frequent drug administration, thereby reducing the pill burden on patients. This thesis evaluates the development of novel subcutaneous implantable devices designed for the improved treatment of chronic conditions, offering long-acting release of various drugs. Monolithic implants loaded with olanzapine (OLZ) as a model drug were produced using robocasting 3D printing technology and demonstrated promising in vitro release rates for the treatment of schizophrenia. Different polymers were assessed, resulting in varying drug release durations. To further prolong drug delivery, polymeric coatings were explored. Additionally, the manufacturing process for the polymeric films was refined, resulting in the production of polymeric tubes. These tubes were loaded with Tizanidine (TZ) pellets to evaluate the performance of the new devices. The pellets were developed using two techniques: direct compression and vacuum compression with heat. The proposed implants are formulated using bioresorbable polymers, eliminating the need for removal once the drug is depleted. Furthermore, all physicochemical characterizations of the implants were performed using techniques such as microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction, among others. Drug release studies were conducted using reverse-phase high-performance liquid chromatography (RP-HPLC) to quantify the amount of drug released from the implant. Chronic conditions are responsible for three out of every five deaths worldwide. Innovation is essential to alleviate the burden of chronic diseases. The implants developed in this thesis not only encourage better patient adherence to medication but also offer a simple technology that provides local anaesthesia following implant insertion.

Thesis embargoed until 31 December 2026.

Date of Award	Dec 2024
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Eneko Larrañeta (Supervisor) & Ryan Donnelly (Supervisor)