Washing away the sile

Abstract

Drug delivery to anatomically complex and physiologically protected regions of the body remains a major challenge in pharmaceutical science. In the inner ear, the blood-labyrinth barrier significantly limits the efficacy of systemically administered drugs. As a result, conditions such as sensorineural hearing loss, Ménière's disease, and tinnitus are often treated suboptimally due to poor drug bioavailability and the side effects of high systemic doses. Localized drug delivery systems present a promising alternative, offering targeted and sustained release directly at the site of pathology. Recent advances in 3D printing technologies have accelerated the development of such systems by enabling the fabrication of drug delivery platforms with customizable geometries and controlled release profiles. While the fabrication of these systems has become increasingly accessible, challenges remain in ensuring their functional performance, drug compatibility, and reproducibility. Many studies have aimed to harness the resolution and precision of additive manufacturing (AM) to fine-tune pharmacokinetics, but limitations persist, particularly regarding the low rates of drug release and insufficient material characterization. Among the emerging AM techniques, two-photon polymerization (2PP) stands out for its ability to produce microscale structures with sub-micron resolution. This capability allows for the fabrication of platforms that, in principle, can accommodate a wide range of pharmaceutical compounds, opening new possibilities for site-specific therapies in the inner ear. This thesis addresses a critical clinical need by exploring the potential of 2PP for the fabrication of cochlea-specific drug delivery systems.