Biodegradable Intra-arterial Devices for Focal Drug Delivery to Targeted Organs

Abstract

This study presents the development of biodegradable intra-arterial drug delivery (IADD) devices for the focal treatment of targeted organs. The IADD devices are fabricated using magnesium (Mg) and poly(glycerol sebacate) (PGS), leveraging their biocompatibility and tunable biodegradability, and are loaded with two model drugs, dexamethasone (DEX) or cisplatin (CIS). The IADD devices with helical and linear designs were fabricated for focal drug delivery to targeted organs and characterized for their microstructure and composition using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). The results confirmed the successful incorporation and stability of the drugs within the device. The IADD devices demonstrated in vitro release of DEX and CIS over 30 days, with drug-dependent and fabrication-dependent release profiles. The IADD devices demonstrated cytocompatibility with endothelial cells and sustained pharmacological activity against glioma cells throughout the in vitro release period. DEX-loaded IADD devices were implanted into the artery upstream of a target organ in rat models. The devices implanted into the renal artery to target the kidney and the carotid artery to target the brain achieved 109-fold and 68-fold improvements, respectively, in organ vs systemic drug levels compared to oral drug administration. Arterial histology and explanted-device analysis provided preliminary evidence of local vascular tolerability and device integrity over the examined implantation period. Overall, these results support IADD devices as a proof-of-concept approach for focal intra-arterial drug delivery to targeted organs, demonstrating substantially elevated target-organ drug levels relative to systemic exposure. HighlightsO_LIIntroduction of a novel intra-arterial drug delivery (IADD) platform C_LIO_LIIADD devices were fabricated from bioresorbable Mg and drug-loaded PGS C_LIO_LIDEX- and CIS-loaded IADD devices were evaluated for in vitro release and bioactivity C_LIO_LIIADD delivery achieved marked DEX enrichment in the kidney and brain C_LIO_LIPost-implantation studies support preliminary vascular safety C_LI