Development of biodegradable implants for sustained drug delivery

Abstract

The advent of sustained drug delivery has resulted in many patient benefits including reduced frequency of drug administration and reduced side effects. Implantable drug delivery benefits from these advantages, but importantly, can be removed if adverse effects necessitate it. In this thesis, reservoir and matrix-type subcutaneous implants were produced and demonstrated adjustable release rates for several compounds. Reservoir-type implants were produced using 3D printing and showed promising and adjustable in vitro release rates for model compounds: methylene blue, ibuprofen sodium and ibuprofen free acid. These implants could be promising for localised delivery of chemotherapeutics, antibiotics, or anaesthetics. However, they were not prolonged enough for the treatment of chronic diseases (for example human immunodeficiency virus). Polymeric coatings were developed which prolonged the release from these implants and increased their potential as a drug delivery device for chronic conditions. Sterilisation is an important factor which must be considered when designing a new implantable device. Gamma radiation, microwave radiation and ultraviolet light were investigated as potential sterilisation methods for polymeric implants. Microwave radiation proved to be an ineffective sterilisation method. However, gamma radiation and ultraviolet light showed promise. Matrix-type implants containing levothyroxine sodium were fabricated using solvent casting and demonstrated promising in vitro release rates for the treatment of hypothyroidism (a common condition which can have debilitating side effects and result in high costs to the health service or patient if not managed effectively). The implants produced in this work have the potential to improve the treatment outcomes and quality of life of patients with hypothyroidism. The simple implantable devices produced in this thesis are easily prepared and have the potential to be applied to a wide range of drug compounds and clinical conditions. This simplicity also gives them potential to be used in the on demand production of personalised drug delivery devices.

Date of Award	Jul 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy
Supervisor	Eneko Larrañeta (Supervisor), Ryan Donnelly (Supervisor) & Juan Dominguez Robles (Supervisor)