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

This study presents the development of biodegradable intra-arterial drug delivery (IADD) devices for focal treatment of targeted organs, to enhance therapeutic efficacy while minimizing systemic toxicity. 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, i.e., 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 a sustained release of DEX and CIS over 30 days in vitro, with cumulative release of 373.11 {+/-} 1.41 {micro}g and 64.73 {+/-} 0.06 {micro}g, respectively. The IADD devices demonstrated cytocompatibility with endothelial cells and sustained pharmacological activity against glioma cells throughout the in vitro release period. We implanted DEX-loaded IADD devices 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. These results proved the safety and efficacy of the IADD devices for sustained, focal drug delivery of different drugs to the target organs, with reduced systemic drug exposure. Overall, the results demonstrated the potential of the IADD devices as a valuable platform technology to achieve focal drug delivery to targeted organs for a wide range of clinical applications, especially for delivering drugs with high efficacy, high systemic side-effects, and narrow therapeutic window.