Development of implantable devices for sustained drug delivery of schizophrenia treatment

Abstract

Schizophrenia is a common, severe, and complex chronic mental illness with a prevalence of approximately 0.32% and a 5.6% lifetime probability of suicide. To control the symptoms and minimize the frequency and severity of relapses, patients with schizophrenia require lifelong treatment with antipsychotic drugs. Risperidone (RIS) and Paliperidone (PPD) are both atypical antipsychotic drugs commonly prescribed to treat schizophrenia. Both medications are available as oral tablets. As a result, the medication is subject to enzymatic degradation and first-pass metabolism in the digestive system. Moreover, adherence to prescribed medication is one of the most challenging aspects of treatment. In the short term (1 year), around half (41.7%) of patients do not adhere to the prescribed treatment. In the long run, this number is even higher. Although there are long-acting injectable forms of both medications to improve patient compliance, the injections are painful and invasive; furthermore, healthcare professionals are required to administer them. To overcome these challenges, microneedle (MN) systems containing RIS or PPD and implants containing RIS have been developed. MNs are minimally invasive dosage forms that can be self-administered by patients. Following transdermal insertion, drugs can be delivered into the systemic circulation to exert their effects. Implantable drug delivery systems (IDDS) are typically medical devices that can steadily deliver drugs to a specific site of action or into the systemic circulation. Although long-acting injections also offer benefits such as higher adherence and improved bioavailability, IDDS, unlike injectables, may be removed from the body if adverse effects occur. Moreover, due to the solid form of the medications, solid implants may be more stable than long-acting injections. In this study, MNs and implants containing RIS were developed and characterized. Additionally, the plasma pharmacokinetics of both systems were evaluated through in vivo studies. The relevant plasma concentration was achieved during the study period, providing evidence of the feasibility of these novel drug delivery systems and the successful delivery of RIS into the systemic circulation. On this basis, clinical studies are crucial to ensure the safety of these medications and their acceptability to patients before they are translated to the market.

Thesis is embargoed until 31st December 2026.

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